Mobile website
Issue 11,2025 Table of Contents
2025, 32(11):1105-1114.
DOI: 10.3872/j.issn.1007-385X.2025.11.001
Abstract:
[Abstract] Immune checkpoint inhibitors (ICIs) have been widely used in the treatment of various solid tumors, and the fine typing of circulating T lymphocyte subsets has attracted considerable attention due to its potential as a predictive biomarker for treatment efficacy. Currently, commonly used ICI efficacy predictive biomarkers mostly rely on tumor tissue samples, with limitations such as difficulty in sampling and dynamic monitoring. In contrast, the fine typing of circulating T lymphocyte subsets can not only reflect the functional status of T cells to predict the response to ICI treatment but also serve as a feasible dynamic detection method due to its advantages of convenience in sampling and minimal invasiveness. Based on its functional status, the fine typing of circulating T lymphocyte subsets can be mainly classified into activated, proliferative, senescent, and exhausted phenotypes. The activated and proliferative phenotypes usually indicate the activation, proliferation, and functional activation status of T cells, while the senescent and exhausted phenotypes reflect the state of T cells with reduced reserves, decreased proliferative and survival capacities, shortened lifespan, and impaired or incompetent effector functions. These functional states are closely related to the efficacy of ICIs. This article will systematically review the latest research progress in the application of fine typing based on the functional status of peripheral blood T cells in predicting ICI treatment efficacy, explore the predictive value of different functional states, and discuss the clinical application prospects and practical difficulties of this approach as a potential predictive tool, providing references for subsequent technical optimization and clinical transformation.
[Abstract] Immune checkpoint inhibitors (ICIs) have been widely used in the treatment of various solid tumors, and the fine typing of circulating T lymphocyte subsets has attracted considerable attention due to its potential as a predictive biomarker for treatment efficacy. Currently, commonly used ICI efficacy predictive biomarkers mostly rely on tumor tissue samples, with limitations such as difficulty in sampling and dynamic monitoring. In contrast, the fine typing of circulating T lymphocyte subsets can not only reflect the functional status of T cells to predict the response to ICI treatment but also serve as a feasible dynamic detection method due to its advantages of convenience in sampling and minimal invasiveness. Based on its functional status, the fine typing of circulating T lymphocyte subsets can be mainly classified into activated, proliferative, senescent, and exhausted phenotypes. The activated and proliferative phenotypes usually indicate the activation, proliferation, and functional activation status of T cells, while the senescent and exhausted phenotypes reflect the state of T cells with reduced reserves, decreased proliferative and survival capacities, shortened lifespan, and impaired or incompetent effector functions. These functional states are closely related to the efficacy of ICIs. This article will systematically review the latest research progress in the application of fine typing based on the functional status of peripheral blood T cells in predicting ICI treatment efficacy, explore the predictive value of different functional states, and discuss the clinical application prospects and practical difficulties of this approach as a potential predictive tool, providing references for subsequent technical optimization and clinical transformation.
2025, 32(11):1115-1120.
DOI: 10.3872/j.issn.1007-385X.2025.11.002
Abstract:
[Abstract] Objective: To investigate the impact of indoleamine 2,3-dioxygenase (IDO) inhibitor 1-L-methyltryptophan (1-L-MT) on dendritic cell (DC) function and the therapeutic efficacy of combining IDO inhibition with DC vaccination against colorectal cancer. Methods: IDO expression in DCs was determined by WB assay. After treatment with 1-L-MT, phenotypic changes in DC surface markers were analysed by flow cytometry. Antigen-pulsed DCs pretreated with 1-L-MT were co-cultured with T cells. The subsequent T cell response was analyzed to evaluate the effect of 1-L-MT on the capacity of DCs to induce antigen-specific T cell proliferation and to modulate the CD8? T cell proportion. In vitro cytotoxicity assays evaluated the tumoricidal activity of 1-L-MT–modulated DC-induced antigen-specific T cells against the colorectal cancer cell line CT26. A murine tumor-bearing model was established to assess the safety and antitumor efficacy of combined 1-L-MT and DC vaccination. Results: DCs constitutively expressed IDO protein. Following 1-L-MT treatment, the maturation marker CD40 was significantly up-regulated (P < 0.05). DCs exposed to 1-L-MT exhibited enhanced capacity to promote antigen-specific T-cell proliferation (P < 0.01), increased CD8? T-cell proportion (P < 0.05), and potentiated specific lysis of CT26 tumor cells (P < 0.01). In vivo, combined 1-L-MT and DC vaccine markedly suppressed tumor growth (P < 0.01) and prolonged survival (P < 0.05). Conclusion: 1-L-MT promotes DC maturation and enhances their immune-activating function by boosting T cell activation. Combined with DC vaccination, it significantly amplifies antigen-specific T-cell responses, restrains colorectal cancer progression, and extends survival, indicating promising clinical translational potential.
[Abstract] Objective: To investigate the impact of indoleamine 2,3-dioxygenase (IDO) inhibitor 1-L-methyltryptophan (1-L-MT) on dendritic cell (DC) function and the therapeutic efficacy of combining IDO inhibition with DC vaccination against colorectal cancer. Methods: IDO expression in DCs was determined by WB assay. After treatment with 1-L-MT, phenotypic changes in DC surface markers were analysed by flow cytometry. Antigen-pulsed DCs pretreated with 1-L-MT were co-cultured with T cells. The subsequent T cell response was analyzed to evaluate the effect of 1-L-MT on the capacity of DCs to induce antigen-specific T cell proliferation and to modulate the CD8? T cell proportion. In vitro cytotoxicity assays evaluated the tumoricidal activity of 1-L-MT–modulated DC-induced antigen-specific T cells against the colorectal cancer cell line CT26. A murine tumor-bearing model was established to assess the safety and antitumor efficacy of combined 1-L-MT and DC vaccination. Results: DCs constitutively expressed IDO protein. Following 1-L-MT treatment, the maturation marker CD40 was significantly up-regulated (P < 0.05). DCs exposed to 1-L-MT exhibited enhanced capacity to promote antigen-specific T-cell proliferation (P < 0.01), increased CD8? T-cell proportion (P < 0.05), and potentiated specific lysis of CT26 tumor cells (P < 0.01). In vivo, combined 1-L-MT and DC vaccine markedly suppressed tumor growth (P < 0.01) and prolonged survival (P < 0.05). Conclusion: 1-L-MT promotes DC maturation and enhances their immune-activating function by boosting T cell activation. Combined with DC vaccination, it significantly amplifies antigen-specific T-cell responses, restrains colorectal cancer progression, and extends survival, indicating promising clinical translational potential.
2025, 32(11):1121-1127.
DOI: 10.3872/j.issn.1007-385X.2025.11.003
Abstract:
[Abstract] Objective: To construct patient-derived organoid (PDO) models of cholangiocarcinoma (CCA) and evaluate their application values in assessing the drug sensitivity to cisplatin and gemcitabine, both as single agents and in combination. Methods: TTumor tissues were collected from four patients with pathologically confirmed cholangiocarcinoma who had not received any prior systematic treatment. PDO models were constructed using matrigel 3D cultures. The consistency of histological morphology and genetic characteristics between PDO and primary tumors was validated by hematoxylin-eosin (H-E) staining, immunohistochemistry (IHC) and whole-exome sequencing (WES). Drug sensitivity of stably passaged PDO was detected using the adenosine triphosphate (ATP) assay, and dose-response curves were used to calculate the half-maximal inhibitory concentration (IC50 ). Synergistic effects were evaluated by calculating the combination index (CI) through the Chou-Talalay method. Results: PDO models for three CCA strains capable of stable subculturing for over seven generations were successfully constructed. H-E staining and IHC results demonstrated high consistency between the PDO models and the primary tumors. WES analysis revealed that the paired PDO retained approximately 78.4% of the genetic variations present in the source tissues. The IC50 values of the three PDO for cisplatin were (277.50 ± 4.056), (9.129 0 ± 1.012), and (115.50 ± 3.034) μmol/L, respectively, while the IC50 values for gemcitabine were (0.581 8 ± 0.020), (0.012 1 ± 0.008), and (0.048 9 ± 0.004) μmol/L, indicating significant inter-individual differences. In the combination therapy experiment, PDO#1 exhibited a significant synergistic effect (CI = 0.116-0.573); PDO#2 showed antagonism at low doses and synergy at moderate doses; PDO#3 displayed antagonism at low doses, synergy at moderate doses, and a return to antagonism at high doses (CI ≈ 1.99 in the highest concentration group). These results indicated that the synergistic effect of the drug combination was strictly confined to a specific dose range. Conclusion: The CCA PDO model faithfully reproduces the morphological and genetic features of the original tumor, and effectively simulates the heterogeneous drug response patterns in patients' tumors, which provides an efficient and reliable platform for selecting and optimizing personalized clinical treatment strategies.
[Abstract] Objective: To construct patient-derived organoid (PDO) models of cholangiocarcinoma (CCA) and evaluate their application values in assessing the drug sensitivity to cisplatin and gemcitabine, both as single agents and in combination. Methods: TTumor tissues were collected from four patients with pathologically confirmed cholangiocarcinoma who had not received any prior systematic treatment. PDO models were constructed using matrigel 3D cultures. The consistency of histological morphology and genetic characteristics between PDO and primary tumors was validated by hematoxylin-eosin (H-E) staining, immunohistochemistry (IHC) and whole-exome sequencing (WES). Drug sensitivity of stably passaged PDO was detected using the adenosine triphosphate (ATP) assay, and dose-response curves were used to calculate the half-maximal inhibitory concentration (IC50 ). Synergistic effects were evaluated by calculating the combination index (CI) through the Chou-Talalay method. Results: PDO models for three CCA strains capable of stable subculturing for over seven generations were successfully constructed. H-E staining and IHC results demonstrated high consistency between the PDO models and the primary tumors. WES analysis revealed that the paired PDO retained approximately 78.4% of the genetic variations present in the source tissues. The IC50 values of the three PDO for cisplatin were (277.50 ± 4.056), (9.129 0 ± 1.012), and (115.50 ± 3.034) μmol/L, respectively, while the IC50 values for gemcitabine were (0.581 8 ± 0.020), (0.012 1 ± 0.008), and (0.048 9 ± 0.004) μmol/L, indicating significant inter-individual differences. In the combination therapy experiment, PDO#1 exhibited a significant synergistic effect (CI = 0.116-0.573); PDO#2 showed antagonism at low doses and synergy at moderate doses; PDO#3 displayed antagonism at low doses, synergy at moderate doses, and a return to antagonism at high doses (CI ≈ 1.99 in the highest concentration group). These results indicated that the synergistic effect of the drug combination was strictly confined to a specific dose range. Conclusion: The CCA PDO model faithfully reproduces the morphological and genetic features of the original tumor, and effectively simulates the heterogeneous drug response patterns in patients' tumors, which provides an efficient and reliable platform for selecting and optimizing personalized clinical treatment strategies.
2025, 32(11):1128-1135.
DOI: 10.3872/j.issn.1007-385X.2025.11.004
Abstract:
[Abstract] Objective: To prepare and characterize indocyanine green (ICG)-loaded F127 nanomicelles (F127-ICG) and explore their anti-tumor effects through their photothermal effect, antigen-capturing capability, and lymph node (LN)-targeting properties. Methods: F127-ICG was prepared using the thin-film hydration method. The particle size and Zeta potential were measured using a Malvern particle size analyzer. The absorption and fluorescence spectra were determined using ultraviolet-visible and fluorescence spectrophotometry, respectively. The antigen-capturing capability of F127-ICG was analyzed by comparing the basic properties and protein content changes of F127 nanomicelles before and after incubation with tumor cell lysates. The photothermal cytotoxicity of F127-ICG against breast cancer cells (4T1) was evaluated using a Calcein-AM/PI double-staining assay. Dye-labeled F127 nanomicelles were subcutaneously injected into mice to establish a lymphatic drainage model. The LN targeting ability of F127 nanomicelles was detected using in vivo small animal imaging, and the accumulation and penetration of F127 nanomicelles in the inguinal and axillary lymph nodes of mice were detected by ex vivo organ imaging. A bilateral breast cancer model was established on the back of the mouse, and F127-ICG was injected intratumorally for photothermal therapy (PTT). Meanwhile, the growth of the contralateral tumor was monitored. Results: The F127-ICG nanomicelles were successfully prepared, with a mean particle size of (19.41 ± 0.49) nm and an average Zeta potential of –(2.78 ± 0.36) mV. After co-incubation of F127-ICG with tumor antigens, the particle size, Zeta potential negativity, and protein content all increased (P < 0.05). The results of the Calcein-AM/PI double staining assay revealed that F127-ICG could effectively exert a photothermal effect to mediate the killing of 4T1 cells. In vivo imaging results revealed that F127 nanomicelles can effectively target LN. In animal experiments, the contralateral tumor volume in the F127-ICG + Laser group was smaller than that in the PBS and F127-ICG groups (P < 0.05). Conclusion: F127-ICG-mediated photothermal effects can effectively ablate primary tumors and capture released tumor-specific antigens and then migrate to local LN, which promotes anti tumor immune response, inhibits distant tumor growth, and enhances in situ vaccine efficacy.
[Abstract] Objective: To prepare and characterize indocyanine green (ICG)-loaded F127 nanomicelles (F127-ICG) and explore their anti-tumor effects through their photothermal effect, antigen-capturing capability, and lymph node (LN)-targeting properties. Methods: F127-ICG was prepared using the thin-film hydration method. The particle size and Zeta potential were measured using a Malvern particle size analyzer. The absorption and fluorescence spectra were determined using ultraviolet-visible and fluorescence spectrophotometry, respectively. The antigen-capturing capability of F127-ICG was analyzed by comparing the basic properties and protein content changes of F127 nanomicelles before and after incubation with tumor cell lysates. The photothermal cytotoxicity of F127-ICG against breast cancer cells (4T1) was evaluated using a Calcein-AM/PI double-staining assay. Dye-labeled F127 nanomicelles were subcutaneously injected into mice to establish a lymphatic drainage model. The LN targeting ability of F127 nanomicelles was detected using in vivo small animal imaging, and the accumulation and penetration of F127 nanomicelles in the inguinal and axillary lymph nodes of mice were detected by ex vivo organ imaging. A bilateral breast cancer model was established on the back of the mouse, and F127-ICG was injected intratumorally for photothermal therapy (PTT). Meanwhile, the growth of the contralateral tumor was monitored. Results: The F127-ICG nanomicelles were successfully prepared, with a mean particle size of (19.41 ± 0.49) nm and an average Zeta potential of –(2.78 ± 0.36) mV. After co-incubation of F127-ICG with tumor antigens, the particle size, Zeta potential negativity, and protein content all increased (P < 0.05). The results of the Calcein-AM/PI double staining assay revealed that F127-ICG could effectively exert a photothermal effect to mediate the killing of 4T1 cells. In vivo imaging results revealed that F127 nanomicelles can effectively target LN. In animal experiments, the contralateral tumor volume in the F127-ICG + Laser group was smaller than that in the PBS and F127-ICG groups (P < 0.05). Conclusion: F127-ICG-mediated photothermal effects can effectively ablate primary tumors and capture released tumor-specific antigens and then migrate to local LN, which promotes anti tumor immune response, inhibits distant tumor growth, and enhances in situ vaccine efficacy.
2025, 32(11):1136-1142.
DOI: 10.3872/j.issn.1007-385X.2025.11.005
Abstract:
[Abstract] Objective: To investigate cytochrome c oxidase subunit 7A2, mitochondrial (COX7A2) expression in bladder cancer cells, and the effects of its combination with cisplatin on the proliferation, apoptosis, and mitochondrial function of bladder cancer J82 cells. Methods: Bioinformatics analysis was used to assess COX7A2 expression in bladder cancer patients, with validation in the J82 cell. Functional experiments included four groups: the Control group (siNC transfection only), the siRNA group (COX7A2 siRNA transfection only), the Control + Cisplatin group (siNC transfection followed by cisplatin), and the siRNA + Cisplatin group (COX7A2 knockdown followed by cisplatin). CCK-8, Transwell migration assay, and colony formation assay detected the proliferation and migration abilities in the Control and siRNA groups. The ATP level, the ROS level, and MMP of cells in each group were detected using corresponding kits to assess mitochondrial function. Flow cytometry detected cell apoptosis in each group to reveal the responsive relationship between mitochondrial status and cisplatin treatment. Furthermore, the Cancer Treatment Response gene signature Database (CTR-DB) was utilized to analyze the correlation between COX7A2 expression and the prognosis of bladder cancer patients receiving cisplatin-based combination therapy. Results: Bioinformatics analysis and survival curves showed that COX7A2 was highly expressed in bladder cancer patients and was associated with poor prognosis. COX7A2 was significantly overexpressed in J82 cells (P < 0.05). Without cisplatin treatment, compared with the Control group, the siRNA group exhibited significantly decreased abilities in the proliferation, migration, and colony formation of J82 cells (all P < 0.001). Mitochondrial ATP expression decreased (P < 0.01); ROS expression levels increased (P < 0.000 1); MMP depolarized (P < 0.000 1), and the apoptosis levels increased (P < 0.05). After cisplatin treatment, compared with the Control + Cisplatin group, the siRNA + Cisplatin group showed decreased ATP expression (P < 0.01), increased ROS expression levels (P < 0.000 1), MMP depolarization (P < 0.000 1), impaired mitochondrial function, and increased apoptosis levels (P < 0.001). Bioinformatic analysis of the CTR-DB dataset indicated that among five bladder cancer patients receiving combination therapy of cisplatin, doxorubicin, methotrexate, and vincristine, responders had lower median COX7A2 RNA expression than non-responders (median expression: 4 501 vs 5 009). Similarly, among 12 bladder cancer patients receiving platinum-based combination therapies, responders showed lower median COX7A2 RNA expression than non-responders (median expression: 2 947 vs 3 035). However, due to the limited sample size, although a trend was observed, it did not reach statistical significance. Conclusion: Knockdown of COX7A2 can inhibit the proliferation and migration of bladder cancer cells by impairing mitochondrial function, and may thereby enhance cellular sensitivity to cisplatin-induced apoptosis.
[Abstract] Objective: To investigate cytochrome c oxidase subunit 7A2, mitochondrial (COX7A2) expression in bladder cancer cells, and the effects of its combination with cisplatin on the proliferation, apoptosis, and mitochondrial function of bladder cancer J82 cells. Methods: Bioinformatics analysis was used to assess COX7A2 expression in bladder cancer patients, with validation in the J82 cell. Functional experiments included four groups: the Control group (siNC transfection only), the siRNA group (COX7A2 siRNA transfection only), the Control + Cisplatin group (siNC transfection followed by cisplatin), and the siRNA + Cisplatin group (COX7A2 knockdown followed by cisplatin). CCK-8, Transwell migration assay, and colony formation assay detected the proliferation and migration abilities in the Control and siRNA groups. The ATP level, the ROS level, and MMP of cells in each group were detected using corresponding kits to assess mitochondrial function. Flow cytometry detected cell apoptosis in each group to reveal the responsive relationship between mitochondrial status and cisplatin treatment. Furthermore, the Cancer Treatment Response gene signature Database (CTR-DB) was utilized to analyze the correlation between COX7A2 expression and the prognosis of bladder cancer patients receiving cisplatin-based combination therapy. Results: Bioinformatics analysis and survival curves showed that COX7A2 was highly expressed in bladder cancer patients and was associated with poor prognosis. COX7A2 was significantly overexpressed in J82 cells (P < 0.05). Without cisplatin treatment, compared with the Control group, the siRNA group exhibited significantly decreased abilities in the proliferation, migration, and colony formation of J82 cells (all P < 0.001). Mitochondrial ATP expression decreased (P < 0.01); ROS expression levels increased (P < 0.000 1); MMP depolarized (P < 0.000 1), and the apoptosis levels increased (P < 0.05). After cisplatin treatment, compared with the Control + Cisplatin group, the siRNA + Cisplatin group showed decreased ATP expression (P < 0.01), increased ROS expression levels (P < 0.000 1), MMP depolarization (P < 0.000 1), impaired mitochondrial function, and increased apoptosis levels (P < 0.001). Bioinformatic analysis of the CTR-DB dataset indicated that among five bladder cancer patients receiving combination therapy of cisplatin, doxorubicin, methotrexate, and vincristine, responders had lower median COX7A2 RNA expression than non-responders (median expression: 4 501 vs 5 009). Similarly, among 12 bladder cancer patients receiving platinum-based combination therapies, responders showed lower median COX7A2 RNA expression than non-responders (median expression: 2 947 vs 3 035). However, due to the limited sample size, although a trend was observed, it did not reach statistical significance. Conclusion: Knockdown of COX7A2 can inhibit the proliferation and migration of bladder cancer cells by impairing mitochondrial function, and may thereby enhance cellular sensitivity to cisplatin-induced apoptosis.
GUO Hongyan
,
LI Genghui
,
LIU Bo
,
SUN Xiaojie
,
ZHAO Zhenglin
,
ZHAO Xuemei
,
YANG Chao
,
GAO Han
,
ZHAO Dan
2025, 32(11):1143-1150.
DOI: 10.3872/j.issn.1007-385X.2025.11.006
Abstract:
[Abstract] Objective: To investigate the effects of long non-coding RNA LINC00511 (LINC00511) knockdown on the proliferation, apoptosis, invasion, and other malignant biological behaviors of non-small cell lung cancer (NSCLC) cells through bioinformatics analysis, in vivo and in vitro experiments, and to preliminarily explore its underlying mechanisms. Methods: The gene Expression profiling Interaction analysis (GEPIA) database was used to analyze the expression level of LINC00511 in NSCLC, and its correlation with clinical characteristics such as tumor stage and survival period of patients, as well as genes related to the malignant biological behaviors of tumor cells. The H1299 lung cancer cell line with LINC00511 knockdown was constructed using shRNA lentiviral vectors. The effects on the proliferation, migration, cell cycle and apoptosis of H1299 cells were detected by clone formation assay, scratch healing assay and flow cytometry, respectively. The expressions of related regulatory genes were detected by qRT-PCR, and the expressions of tumor-related proteins were detected by WB assay. A subcutaneous transplanted tumor model was constructed in nude mice, and the tumor tissues were taken for immunohistochemical experiments to detect the expression of Ki67. Results: GEPIA database analysis showed that the expression level of LINC00511 was elevated in NSCLC tissues and correlated with the clinical stage of the disease (P < 0.05). LINC00511 was correlated with the expressions of CASP, CCNB1, CDK4 and other genes in lung cancer (P < 0.01). Knockdown of LINC00511 could inhibit cell colony formation and migration abilities, promote the apoptosis of lung cancer cells, and affect cell cycle progression (P < 0.05, P < 0.01). LINC00511 knockdown could down-regulate the expressions of CCNB, CDK4 and TGF-β1 genes in lung cancer cells (P < 0.01), but had no significant effect on the expressions of CCND1 and VEGFA genes. LINC00511 knockdown could inhibit the expressions of MMP9 and CTNNB1, and up-regulated the expression of CASP3 (P < 0.05, P < 0.01). In vivo experiments in nude mice confirmed that LINC00511 knockdown could inhibit Ki67 expression in transplanted tumor tissues (P < 0.01). Conclusion: LINC00511 is highly expressed in non-small cell lung cancer tissues and is correlated with the clinical stage of lung cancer and the expressions of multiple genes. LINC00511 Knockdown of LINC00511 can inhibit the malignant biological behaviors of lung cancer H1299 cells by affecting the expressions of related genes and proteins.
[Abstract] Objective: To investigate the effects of long non-coding RNA LINC00511 (LINC00511) knockdown on the proliferation, apoptosis, invasion, and other malignant biological behaviors of non-small cell lung cancer (NSCLC) cells through bioinformatics analysis, in vivo and in vitro experiments, and to preliminarily explore its underlying mechanisms. Methods: The gene Expression profiling Interaction analysis (GEPIA) database was used to analyze the expression level of LINC00511 in NSCLC, and its correlation with clinical characteristics such as tumor stage and survival period of patients, as well as genes related to the malignant biological behaviors of tumor cells. The H1299 lung cancer cell line with LINC00511 knockdown was constructed using shRNA lentiviral vectors. The effects on the proliferation, migration, cell cycle and apoptosis of H1299 cells were detected by clone formation assay, scratch healing assay and flow cytometry, respectively. The expressions of related regulatory genes were detected by qRT-PCR, and the expressions of tumor-related proteins were detected by WB assay. A subcutaneous transplanted tumor model was constructed in nude mice, and the tumor tissues were taken for immunohistochemical experiments to detect the expression of Ki67. Results: GEPIA database analysis showed that the expression level of LINC00511 was elevated in NSCLC tissues and correlated with the clinical stage of the disease (P < 0.05). LINC00511 was correlated with the expressions of CASP, CCNB1, CDK4 and other genes in lung cancer (P < 0.01). Knockdown of LINC00511 could inhibit cell colony formation and migration abilities, promote the apoptosis of lung cancer cells, and affect cell cycle progression (P < 0.05, P < 0.01). LINC00511 knockdown could down-regulate the expressions of CCNB, CDK4 and TGF-β1 genes in lung cancer cells (P < 0.01), but had no significant effect on the expressions of CCND1 and VEGFA genes. LINC00511 knockdown could inhibit the expressions of MMP9 and CTNNB1, and up-regulated the expression of CASP3 (P < 0.05, P < 0.01). In vivo experiments in nude mice confirmed that LINC00511 knockdown could inhibit Ki67 expression in transplanted tumor tissues (P < 0.01). Conclusion: LINC00511 is highly expressed in non-small cell lung cancer tissues and is correlated with the clinical stage of lung cancer and the expressions of multiple genes. LINC00511 Knockdown of LINC00511 can inhibit the malignant biological behaviors of lung cancer H1299 cells by affecting the expressions of related genes and proteins.
2025, 32(11):1151-1158.
DOI: 10.3872/j.issn.1007-385X.2025.11.007
Abstract:
[Abstract] Objective: To investigate the functional mechanism of bone marrow mesenchymal stem cell (BMSC)-derived exosome lncRNA PTENP1 in bladder cancer progression. Methods: Exosomes from BMSC (BMSC-Exo) were characterized using transmission electron microscopy, nanoparticle tracking analysis (NTA), and WB assay for exosomal markers. The uptake of exosomes derived from BMSC by bladder cancer 5637 cells was confirmed through confocal microscopy. Based on different transfectants, bladder cancer cells (5637 and T24) were divided into groups: control group (no exosomes), BMSC-Exo group, BMSC OE-NC-Exo group, BMSC OE-PTENP1-Exo group, BMSC sh-NC-Exo group, and BMSC sh-PTENP1-Exo group, and co-cultured with respective exosomes (20 μg/mL). The evaluation of cell proliferation, apoptosis, migration, and invasion was conducted using CCK-8, colony formation, flow cytometry, wound healing, and Transwell assays, respectively. The interactions involving miR-17 with PTENP1 and scavenger receptor class A member 5 (SCARA5) were validated using dual luciferase reporter assays, RNA pull-down, and RNA immunoprecipitation (RIP) methods. Results: qRT-PCR showed that BMSC exosomes overexpressing PTENP1 (BMSC OE-PTENP1 Exo) significantly elevated PTENP1 levels in bladder cancer cells (P < 0.01). BMSC OE-PTENP1-Exo inhibited cell proliferation (P < 0.01), migration (P < 0.01), and invasion (P < 0.01), and promoted cell apoptosis (P < 0.01). Furthermore, in vivo experiments showed that BMSC OE-PTENP1-Exo significantly inhibited tumor growth in nude mice (P < 0.01). Conclusion: BMSC-derived exosomal PTENP1 inhibits BC progression by upregulating the expression of SCARA5 via sponging miR-17, providing a potential new therapeutic target for bladder cancer bladder cancer treatment.
[Abstract] Objective: To investigate the functional mechanism of bone marrow mesenchymal stem cell (BMSC)-derived exosome lncRNA PTENP1 in bladder cancer progression. Methods: Exosomes from BMSC (BMSC-Exo) were characterized using transmission electron microscopy, nanoparticle tracking analysis (NTA), and WB assay for exosomal markers. The uptake of exosomes derived from BMSC by bladder cancer 5637 cells was confirmed through confocal microscopy. Based on different transfectants, bladder cancer cells (5637 and T24) were divided into groups: control group (no exosomes), BMSC-Exo group, BMSC OE-NC-Exo group, BMSC OE-PTENP1-Exo group, BMSC sh-NC-Exo group, and BMSC sh-PTENP1-Exo group, and co-cultured with respective exosomes (20 μg/mL). The evaluation of cell proliferation, apoptosis, migration, and invasion was conducted using CCK-8, colony formation, flow cytometry, wound healing, and Transwell assays, respectively. The interactions involving miR-17 with PTENP1 and scavenger receptor class A member 5 (SCARA5) were validated using dual luciferase reporter assays, RNA pull-down, and RNA immunoprecipitation (RIP) methods. Results: qRT-PCR showed that BMSC exosomes overexpressing PTENP1 (BMSC OE-PTENP1 Exo) significantly elevated PTENP1 levels in bladder cancer cells (P < 0.01). BMSC OE-PTENP1-Exo inhibited cell proliferation (P < 0.01), migration (P < 0.01), and invasion (P < 0.01), and promoted cell apoptosis (P < 0.01). Furthermore, in vivo experiments showed that BMSC OE-PTENP1-Exo significantly inhibited tumor growth in nude mice (P < 0.01). Conclusion: BMSC-derived exosomal PTENP1 inhibits BC progression by upregulating the expression of SCARA5 via sponging miR-17, providing a potential new therapeutic target for bladder cancer bladder cancer treatment.
2025, 32(11):1159-1168.
DOI: 10.3872/j.issn.1007-385X.2025.11.008
Abstract:
[Abstract] Objective: To characterize the heterogeneity of B cells in the colorectal cancer (CRC) tumor microenvironment (TME) through single-cell RNA sequencing (scRNA-seq), thereby providing a theoretical foundation for B cell-based prognostic assessment and immunotherapy. Methods: Fresh surgical specimens from patients with primary colorectal cancer (n = 36) were collected and subjected to scRNA-seq. Cell clustering was performed using Seurat (v5.0). Cell differentiation trajectories were analyzed with Monocle3 (v1.3) and scVelo (v0.3.0). Gene Set Enrichment Analysis (GSEA) was employed to identify relevant functional pathways, and the gene regulatory network was constructed using pySCENIC (v0.11.2). Results: 11 functional subtypes were identified from 24 652 B cells and 49 138 plasma cells. Pseudotime analysis revealed a differentiation trajectory of B cells from a naive to a tissue resident state. Stress-adapted B cells were enriched in tumor tissues (10.39%), exhibiting significant activation of the NOD-like receptor signaling pathway and antigen processing and presentation. Tissue-resident B cells accounted for 9.09% of tumor-infiltrating B cells and showed enhanced C-type lectin receptor signaling and endocytosis. Migratory B cells were least abundant in stage Ⅱ tumors (16.42%), with significant enrichment of metabolic pathways such as oxidative phosphorylation. Plasma cells were terminally differentiated, with IgG-type cells predominating in tumor tissues (20.68%). Conclusion: Stress-adapted and tissue-resident B cells may promote immune escape, while migratory B cells potentially exert anti-tumor effects. IgG-type plasma cells appear to be associated with immunosuppression.
[Abstract] Objective: To characterize the heterogeneity of B cells in the colorectal cancer (CRC) tumor microenvironment (TME) through single-cell RNA sequencing (scRNA-seq), thereby providing a theoretical foundation for B cell-based prognostic assessment and immunotherapy. Methods: Fresh surgical specimens from patients with primary colorectal cancer (n = 36) were collected and subjected to scRNA-seq. Cell clustering was performed using Seurat (v5.0). Cell differentiation trajectories were analyzed with Monocle3 (v1.3) and scVelo (v0.3.0). Gene Set Enrichment Analysis (GSEA) was employed to identify relevant functional pathways, and the gene regulatory network was constructed using pySCENIC (v0.11.2). Results: 11 functional subtypes were identified from 24 652 B cells and 49 138 plasma cells. Pseudotime analysis revealed a differentiation trajectory of B cells from a naive to a tissue resident state. Stress-adapted B cells were enriched in tumor tissues (10.39%), exhibiting significant activation of the NOD-like receptor signaling pathway and antigen processing and presentation. Tissue-resident B cells accounted for 9.09% of tumor-infiltrating B cells and showed enhanced C-type lectin receptor signaling and endocytosis. Migratory B cells were least abundant in stage Ⅱ tumors (16.42%), with significant enrichment of metabolic pathways such as oxidative phosphorylation. Plasma cells were terminally differentiated, with IgG-type cells predominating in tumor tissues (20.68%). Conclusion: Stress-adapted and tissue-resident B cells may promote immune escape, while migratory B cells potentially exert anti-tumor effects. IgG-type plasma cells appear to be associated with immunosuppression.
2025, 32(11):1169-1174.
DOI: 10.3872/j.issn.1007-385X.2025.11.009
Abstract:
[Abstract] Objective: To investigate the efficacy and safety of albumin-binding paclitaxel combined with PD-1 inhibitor in the treatment of bone and soft tissue sarcomas after first-line chemotherapy failure. Methods: This retrospective study analyzed patients with advanced bone and soft tissue sarcomas who failed first-line chemotherapy and were treated at the Department of Orthopedic Oncology of Beijing Jishuitan Hospital between August 2017 and August 2020. Patients received combined treatment with albumin binding paclitaxel (125-140 mg/m2 on days 1 and 8) and anti-PD-1 therapy (sintilimab or toripalimab, every 21 days). Efficacy was evaluated every two treatment cycles according to the RECIST 1.1 criteria and adverse reactions were assessed using the NCI-CTC5.0 criteria. Results: A total of 20 patients who completed between 1 to 8 cycles of treatment with a median of 3 cycles were included in the study. All patients were evaluable for responses: 4 patients (20%) achieved complete remission; no partial remissions were observed; 9 patients (45%) had stable disease, and 7 patients (35%) had disease progression. The overall response rate (ORR) was 20%, and the disease control rate (DCR) was 65%. The median progression-free survival (PFS) was 3.0 months. The main adverse reactions during treatment included Grade 2 leukopenia (40%), Grade 1-2 neurotoxicity (20%), and Grade 2 hypothyroidism (10.0%). Conclusion: The combination therapy of albumin-binding paclitaxel and PD-1 inhibitor offers a potential treatment option for patients with advanced bone and soft tissue sarcomas who have failed first-line chemotherapy. The adverse reactions are manageable, and this regimen merits prospective studies with larger samples to further verify its efficacy.
[Abstract] Objective: To investigate the efficacy and safety of albumin-binding paclitaxel combined with PD-1 inhibitor in the treatment of bone and soft tissue sarcomas after first-line chemotherapy failure. Methods: This retrospective study analyzed patients with advanced bone and soft tissue sarcomas who failed first-line chemotherapy and were treated at the Department of Orthopedic Oncology of Beijing Jishuitan Hospital between August 2017 and August 2020. Patients received combined treatment with albumin binding paclitaxel (125-140 mg/m2 on days 1 and 8) and anti-PD-1 therapy (sintilimab or toripalimab, every 21 days). Efficacy was evaluated every two treatment cycles according to the RECIST 1.1 criteria and adverse reactions were assessed using the NCI-CTC5.0 criteria. Results: A total of 20 patients who completed between 1 to 8 cycles of treatment with a median of 3 cycles were included in the study. All patients were evaluable for responses: 4 patients (20%) achieved complete remission; no partial remissions were observed; 9 patients (45%) had stable disease, and 7 patients (35%) had disease progression. The overall response rate (ORR) was 20%, and the disease control rate (DCR) was 65%. The median progression-free survival (PFS) was 3.0 months. The main adverse reactions during treatment included Grade 2 leukopenia (40%), Grade 1-2 neurotoxicity (20%), and Grade 2 hypothyroidism (10.0%). Conclusion: The combination therapy of albumin-binding paclitaxel and PD-1 inhibitor offers a potential treatment option for patients with advanced bone and soft tissue sarcomas who have failed first-line chemotherapy. The adverse reactions are manageable, and this regimen merits prospective studies with larger samples to further verify its efficacy.
2025, 32(11):1175-1180.
DOI: 10.3872/j.issn.1007-385X.2025.11.010
Abstract:
[Abstract] Objective: To investigate the effects of dexamethasone combined with abiraterone on the urodynamic parameters, levels of androgen receptor splice variant 7 (AR-V7) and human homeobox B13 (HoxB13) in peripheral blood circulating tumor cells, and survival prognosis of patients with castration-resistant prostate cancer (CRPC). Methods: Medical records of 114 CRPC patients admitted to our hospital were retrospectively selected. According to the treatment regimen, they were divided into the control group (treated with 0.5 mg dexamethasone, n = 51) and the observation group (treated with 0.5 mg dexamethasone combined with 1 000 mg abiraterone, n = 63). The efficacy, urodynamic parameters, levels of AR-V7 and HoxB13 in peripheral blood circulating tumor cells, and survival prognosis of the two groups were compared. Results: There were 63 patients in the observation group and 51 in the control group. After 8 weeks of treatment, both the disease control rate (42.86% vs 23.53%) and the objective response rate (96.83% vs 86.27%) were significantly higher in the observation group than in the control group (P < 0.05). The maximum urinary flow rate ([14.58 ± 1.02] mL/s vs [11.18 ± 1.16] mL/s) and the average urinary flow rate ([12.92 ± 1.21] mL/s vs ([9.83 ± 0.59] mL/s) were significantly higher in the observation group, while the residual urine volume ([24.12 ± 1.96] mL vs [28.03 ± 1.68] mL) was significantly lower than in the control group (all P < 0.05). The expression levels of AR-V7 mRNA were similar between the observation group (1.78 ± 0.32) and the control group (1.68 ± 0.46), with no statistically significant difference (P > 0.05). However, the expression level of HoxB13 mRNA in the observation group (1.21 ± 0.27) was significantly lower than that in the control group (1.57 ± 0.37) (P < 0.05). The median progression-free survival was significantly longer in the observation group (6.22 months [95% CI: 5.63~ 6.63]) than in the control group (3.66 months [95% CI: 3.01~3.74]) (P < 0.05). The 3-year overall survival rate was 12.70% in the observation group, significantly higher than 0.00% in the control group (P < 0.05). Conclusion: The combination of dexamethasone and abiraterone demonstrates significant efficacy in treating CRPC patients. It can markedly improve urodynamic parameters, downregulate HoxB13 expression in peripheral blood circulating tumor cells without significantly affecting AR-V7 expression, prolong progression-free survival, and increase the 3-year overall survival rate.
[Abstract] Objective: To investigate the effects of dexamethasone combined with abiraterone on the urodynamic parameters, levels of androgen receptor splice variant 7 (AR-V7) and human homeobox B13 (HoxB13) in peripheral blood circulating tumor cells, and survival prognosis of patients with castration-resistant prostate cancer (CRPC). Methods: Medical records of 114 CRPC patients admitted to our hospital were retrospectively selected. According to the treatment regimen, they were divided into the control group (treated with 0.5 mg dexamethasone, n = 51) and the observation group (treated with 0.5 mg dexamethasone combined with 1 000 mg abiraterone, n = 63). The efficacy, urodynamic parameters, levels of AR-V7 and HoxB13 in peripheral blood circulating tumor cells, and survival prognosis of the two groups were compared. Results: There were 63 patients in the observation group and 51 in the control group. After 8 weeks of treatment, both the disease control rate (42.86% vs 23.53%) and the objective response rate (96.83% vs 86.27%) were significantly higher in the observation group than in the control group (P < 0.05). The maximum urinary flow rate ([14.58 ± 1.02] mL/s vs [11.18 ± 1.16] mL/s) and the average urinary flow rate ([12.92 ± 1.21] mL/s vs ([9.83 ± 0.59] mL/s) were significantly higher in the observation group, while the residual urine volume ([24.12 ± 1.96] mL vs [28.03 ± 1.68] mL) was significantly lower than in the control group (all P < 0.05). The expression levels of AR-V7 mRNA were similar between the observation group (1.78 ± 0.32) and the control group (1.68 ± 0.46), with no statistically significant difference (P > 0.05). However, the expression level of HoxB13 mRNA in the observation group (1.21 ± 0.27) was significantly lower than that in the control group (1.57 ± 0.37) (P < 0.05). The median progression-free survival was significantly longer in the observation group (6.22 months [95% CI: 5.63~ 6.63]) than in the control group (3.66 months [95% CI: 3.01~3.74]) (P < 0.05). The 3-year overall survival rate was 12.70% in the observation group, significantly higher than 0.00% in the control group (P < 0.05). Conclusion: The combination of dexamethasone and abiraterone demonstrates significant efficacy in treating CRPC patients. It can markedly improve urodynamic parameters, downregulate HoxB13 expression in peripheral blood circulating tumor cells without significantly affecting AR-V7 expression, prolong progression-free survival, and increase the 3-year overall survival rate.
2025, 32(11):1181-1187.
DOI: 10.3872/j.issn.1007-385X.2025.11.011
Abstract:
[Abstract] Objective: To develop a chimeric costimulatory receptor (CCR) targeting the CD7 antigen and prepare CCR-modified γδ T cells from healthy donors for the evaluation of its in vitro and in vivo cytotoxic effects against T-cell acute lymphoblastic leukemia (T-ALL) cells. Methods: Lentiviral vectors carrying CD7-DAP10-CCR were constructed and γδ T cells in the peripheral blood of healthy individuals were transduced to prepare CCR γδ T cells targeting the CD7 antigen (CD7-DAP10-CCR-γδ T). The obtained cells were expanded in vitro using artificial antigen-presenting cells (aAPC) expressing CD64, CD86, and CD137L. The in vitro cytotoxic effects of CD7-DAP10-CCR-γδ T cells against T-ALL cells (Jurkat), CD7-deficient Jurkat cells (CD7? Jurkat), and healthy donor primary αβ T cells were detected using the Annexin Ⅴ/7-AAD assay. The experiment was performed at three effector-to-target (E∶T) ratios (1∶1, 1∶3, and 1∶10), with Jurkat cells as CD7 positive target cells, CD7? Jurkat cells as CD7 negative target cells to verify the killing specificity, and healthy donor primary αβ T cells as CD7 positive normal control cells to evaluate the off-target effects of CD7 DAP10-CCR-γδ T cells. The incubation time was 18-24 h. Furthermore, the in vivo efficacy was evaluated in an immunodeficient mouse model bearing T-ALL xenografts. In vivo imaging of tumor-bearing immunodeficient mice was regularly conducted, their body weight and length of survival monitored to evaluate in vivo efficacy of CD7-DAP10-CCR-γδ T cells in tumor-bearing immunodeficient mice. Results: CD7-DAP10-CCR-γδ T cells were successfully prepared in vitro using aAPC, achieving an average expansion fold exceeding 10 000. In vitro cytotoxicity assays demonstrated that these cells exhibited significantly high killing activity against T-ALL cells and significantly high toxicity against Jurkat cells (P < 0.01), while showing limited cytotoxicity against CD7? Jurkat cells and negligible effects on normal primary CD7-high αβ T cells. In vivo efficacy experiment on tumor-bearing immunodeficient mice indicated that treatment with CD7-DAP10-CCR-γδ T cells resulted in a significant prolongation of survival compared with the PBS control group. Conclusion: CD7-DAP10-CCR-γδ T cells can be successfully generated in vitro using aAPC. CD7-DAP10-CCR-γδ T cells demonstrate strong cytotoxicity against T-ALL cells both in vitro and in vivo, which suggests therapeutic potential of CD7-DAP10-CCR-γδ T cells against T-ALL cells.
[Abstract] Objective: To develop a chimeric costimulatory receptor (CCR) targeting the CD7 antigen and prepare CCR-modified γδ T cells from healthy donors for the evaluation of its in vitro and in vivo cytotoxic effects against T-cell acute lymphoblastic leukemia (T-ALL) cells. Methods: Lentiviral vectors carrying CD7-DAP10-CCR were constructed and γδ T cells in the peripheral blood of healthy individuals were transduced to prepare CCR γδ T cells targeting the CD7 antigen (CD7-DAP10-CCR-γδ T). The obtained cells were expanded in vitro using artificial antigen-presenting cells (aAPC) expressing CD64, CD86, and CD137L. The in vitro cytotoxic effects of CD7-DAP10-CCR-γδ T cells against T-ALL cells (Jurkat), CD7-deficient Jurkat cells (CD7? Jurkat), and healthy donor primary αβ T cells were detected using the Annexin Ⅴ/7-AAD assay. The experiment was performed at three effector-to-target (E∶T) ratios (1∶1, 1∶3, and 1∶10), with Jurkat cells as CD7 positive target cells, CD7? Jurkat cells as CD7 negative target cells to verify the killing specificity, and healthy donor primary αβ T cells as CD7 positive normal control cells to evaluate the off-target effects of CD7 DAP10-CCR-γδ T cells. The incubation time was 18-24 h. Furthermore, the in vivo efficacy was evaluated in an immunodeficient mouse model bearing T-ALL xenografts. In vivo imaging of tumor-bearing immunodeficient mice was regularly conducted, their body weight and length of survival monitored to evaluate in vivo efficacy of CD7-DAP10-CCR-γδ T cells in tumor-bearing immunodeficient mice. Results: CD7-DAP10-CCR-γδ T cells were successfully prepared in vitro using aAPC, achieving an average expansion fold exceeding 10 000. In vitro cytotoxicity assays demonstrated that these cells exhibited significantly high killing activity against T-ALL cells and significantly high toxicity against Jurkat cells (P < 0.01), while showing limited cytotoxicity against CD7? Jurkat cells and negligible effects on normal primary CD7-high αβ T cells. In vivo efficacy experiment on tumor-bearing immunodeficient mice indicated that treatment with CD7-DAP10-CCR-γδ T cells resulted in a significant prolongation of survival compared with the PBS control group. Conclusion: CD7-DAP10-CCR-γδ T cells can be successfully generated in vitro using aAPC. CD7-DAP10-CCR-γδ T cells demonstrate strong cytotoxicity against T-ALL cells both in vitro and in vivo, which suggests therapeutic potential of CD7-DAP10-CCR-γδ T cells against T-ALL cells.
2025, 32(11):1188-1196.
DOI: 10.3872/j.issn.1007-385X.2025.11.012
Abstract:
[摘 要] 3型树突状细胞（DC3）是从人外周血CD1c+DC亚群中新分离出的一个树突状细胞亚群。其表型与2型树突状细胞 （DC2）和单核细胞均有重叠，但其发育及功能与常规树突状细胞（包括DC1和DC2）存在显著差异。DC3的起源与发育、功能特 性、在疾病中的作用等方面成为当前的研究热点。DC3可分泌IL-1β、IL-6、TNF-α等多种细胞因子，并参与调控T细胞应答。在 肿瘤微环境中，DC3呈现双重作用，一方面通过分泌IL-12、IL-18等激活抗肿瘤免疫，另一方面高表达PD-L1、IL-10等介导免疫抑 制。值得注意的是，DC3与肿瘤浸润的CCR7? DC等亚群存在命名争议。本文综述近年来关于DC3表型、发育、功能及参与肿瘤 免疫调节机制的主要研究进展，以期为深入理解DC3在肿瘤免疫微环境中的调控作用提供新视角。
[摘 要] 3型树突状细胞（DC3）是从人外周血CD1c+DC亚群中新分离出的一个树突状细胞亚群。其表型与2型树突状细胞 （DC2）和单核细胞均有重叠，但其发育及功能与常规树突状细胞（包括DC1和DC2）存在显著差异。DC3的起源与发育、功能特 性、在疾病中的作用等方面成为当前的研究热点。DC3可分泌IL-1β、IL-6、TNF-α等多种细胞因子，并参与调控T细胞应答。在 肿瘤微环境中，DC3呈现双重作用，一方面通过分泌IL-12、IL-18等激活抗肿瘤免疫，另一方面高表达PD-L1、IL-10等介导免疫抑 制。值得注意的是，DC3与肿瘤浸润的CCR7? DC等亚群存在命名争议。本文综述近年来关于DC3表型、发育、功能及参与肿瘤 免疫调节机制的主要研究进展，以期为深入理解DC3在肿瘤免疫微环境中的调控作用提供新视角。
2025, 32(11):1197-1201.
DOI: 10.3872/j.issn.1007-385X.2025.11.013
Abstract:
[摘 要] 结直肠癌（CRC）具有较强的免疫抑制特性与肿瘤可塑性，影响患者对常规放化疗的响应。PIK3CA突变在CRC发生 发展中起关键作用，其通过调控肿瘤微环境（TME）促进肿瘤进展。本文系统归纳了PIK3CA突变通过影响TME中的内皮细胞、 癌症相关成纤维细胞、肿瘤相关巨噬细胞和T细胞等关键细胞，介导免疫抑制和肿瘤恶化的机制。本文进一步指出，针对 PIK3CA的单药联合靶向TME组分抑制剂或COX-2抑制剂、免疫检查点抑制剂等是未来治疗CRC重要的方向之一。本研究旨 在为CRC的靶向药物研发和临床治疗提供新思路。
[摘 要] 结直肠癌（CRC）具有较强的免疫抑制特性与肿瘤可塑性，影响患者对常规放化疗的响应。PIK3CA突变在CRC发生 发展中起关键作用，其通过调控肿瘤微环境（TME）促进肿瘤进展。本文系统归纳了PIK3CA突变通过影响TME中的内皮细胞、 癌症相关成纤维细胞、肿瘤相关巨噬细胞和T细胞等关键细胞，介导免疫抑制和肿瘤恶化的机制。本文进一步指出，针对 PIK3CA的单药联合靶向TME组分抑制剂或COX-2抑制剂、免疫检查点抑制剂等是未来治疗CRC重要的方向之一。本研究旨 在为CRC的靶向药物研发和临床治疗提供新思路。
2025, 32(11):1202-1207.
DOI: 10.3872/j.issn.1007-385X.2025.11.014
Abstract:
[摘 要] 生长分化因子15（GDF15）是介导多种肿瘤耐药的关键因子。它主要通过激活PI3K/AKT-Nrf2等信号通路调控肿瘤 细胞凋亡逃逸与代谢重编程并参与诱导EMT和重塑免疫微环境等机制，使肿瘤细胞的耐药能力增强。尽管GDF15相关信号通 路的多样性及受体依赖性的差异给精准靶向治疗带来了挑战，但GDF15在肿瘤患者血清中的表达显著升高表明了它作为预后标 志物和治疗靶点的较高临床转化潜力。本文整合GDF15与不同信号通路的关联及其在肿瘤耐药中的作用机制后认为，将联合靶 向策略、PROTAC技术的应用以及动态监测体系的建立作为未来研究方向，有望为治疗GDF15介导的肿瘤化疗耐药提供有效方 案，进而提升相关抗耐药治疗的临床应用价值。
[摘 要] 生长分化因子15（GDF15）是介导多种肿瘤耐药的关键因子。它主要通过激活PI3K/AKT-Nrf2等信号通路调控肿瘤 细胞凋亡逃逸与代谢重编程并参与诱导EMT和重塑免疫微环境等机制，使肿瘤细胞的耐药能力增强。尽管GDF15相关信号通 路的多样性及受体依赖性的差异给精准靶向治疗带来了挑战，但GDF15在肿瘤患者血清中的表达显著升高表明了它作为预后标 志物和治疗靶点的较高临床转化潜力。本文整合GDF15与不同信号通路的关联及其在肿瘤耐药中的作用机制后认为，将联合靶 向策略、PROTAC技术的应用以及动态监测体系的建立作为未来研究方向，有望为治疗GDF15介导的肿瘤化疗耐药提供有效方 案，进而提升相关抗耐药治疗的临床应用价值。
联系方式
- 《中国肿瘤生物治疗杂志》
- 1994年创刊
- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
- 邮编：200433
- 电话：021-81871002-22
- 电子邮箱：cjcb@biother.cn
- 网址:http://www.biother.cn
- 刊号：ISSN 1007-385X
- CN 31-1725/R
- 国内定价： ￥20元/册
您是第位访问者
Chinese Journal Of Cancer Biotheray ® 2026 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.
Chinese Journal Of Cancer Biotheray ® 2026 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.