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Volume 32,Issue 10,2025 Table of Contents
2025, 32(10):993-1009.
DOI: 10.3872/j.issn.1007-385X.2025.10.001
Abstract:
[Abstract] Tumor neoantigens are aberrant peptides unique to tumor cells, which can be recognized by the immune system and have become a research hotspot in precision tumor immunotherapy. This article provides an overview of the diverse molecular origins of tumor neoantigens, analyzes the antigen processing and presentation mechanisms of MHC class Ⅰ/Ⅱ molecules, and explores the critical role of cross-presentation in immune recognition. It also analyzes the structural and signal transduction characteristics of the T cell receptor (TCR) complex, emphasizes the importance of immunogenicity evaluation, and elaborates on the progress of high-throughput omics and artificial intelligence/deep learning in neoantigen discovery and the prediction of MHC-peptide and TCR-peptide-MHC interactions. Additionally, it introduces the application prospects and challenges of neoantigen-based therapeutic vaccines and adoptive cell therapy in solid tumors, discusses the limitations of neoantigen prediction, tumor immune escape, and ethical issues, and looks forward to the significance of technologies such as single-cell spatial transcriptomics for immunotherapy design, TCR molecular design, and the construction of a global neoantigen repository.
[Abstract] Tumor neoantigens are aberrant peptides unique to tumor cells, which can be recognized by the immune system and have become a research hotspot in precision tumor immunotherapy. This article provides an overview of the diverse molecular origins of tumor neoantigens, analyzes the antigen processing and presentation mechanisms of MHC class Ⅰ/Ⅱ molecules, and explores the critical role of cross-presentation in immune recognition. It also analyzes the structural and signal transduction characteristics of the T cell receptor (TCR) complex, emphasizes the importance of immunogenicity evaluation, and elaborates on the progress of high-throughput omics and artificial intelligence/deep learning in neoantigen discovery and the prediction of MHC-peptide and TCR-peptide-MHC interactions. Additionally, it introduces the application prospects and challenges of neoantigen-based therapeutic vaccines and adoptive cell therapy in solid tumors, discusses the limitations of neoantigen prediction, tumor immune escape, and ethical issues, and looks forward to the significance of technologies such as single-cell spatial transcriptomics for immunotherapy design, TCR molecular design, and the construction of a global neoantigen repository.
2025, 32(10):1010-1018.
DOI: 10.3872/j.issn.1007-385X.2025.10.002
Abstract:
[Abstract] Objective: To investigate the effects of Wnt5a on the vasculogenic mimicry (VM) and cancer stem cell (CSC) properties of prostate cancer (PCa) cells by upregulating the expression of miR-141-3p. Methods: Human prostate epithelial cell line RWPE-1 and PCa cell lines PC-3, LNCaP, and DU145 were cultured. qPCR was employed to detect miR-141-3p expression, and Western blotting (WB) was used to measure Wnt5a protein levels. Stable Wnt5a-knockdown or miR-141-3p-knockdown LNCaP and DU145 cell lines were established respectively via plasmid transfection. VM formation ability was assessed by three-dimensional culture assay. Cell proliferation ability and drug sensitivity were measured by CCK-8 assay. Cell migration and invasion abilities were detected using wound healing and Transwell assays, respectively. The expressions of VM-related molecules and CSC markers were detected by qPCR and WB. Colony formation ability was determined by clonogenic assay. The proportion of CD133+ cells was sorted and calculated by flow cytometry. The expressions of miR-141-3p and Wnt5a in CD133+ and CD133– cells were detected by qPCR and WB. Stable Wnt5a-overexpressing PCa cell lines were constructed via plasmid transfection. The effects of Wnt5a and different Wnt pathway downstream inhibitors on miR-141-3p expression and promoter activity were detected by qPCR and dual-luciferase reporter assays. Expression of c-Jun was knocked down in Wnt5a-overexpressing cells using si-c-Jun transfection. The target binding relationship between c-Jun and the miR-141-3p promoter was verified by qPCR, dual-luciferase reporter assay, and chromatin immunoprecipitation assay. Results: The expressions of miR-141-3p and Wnt5a were significantly higher in PCa cells compared with those in RWPE-1 cells, with the highest relative expression in DU145 cells and the lowest in LNCaP cells (P < 0.001). Downregulation of Wnt5a or miR-141-3p significantly inhibited VM formation ability and stemness of PCa cells, and significantly suppressed the proliferation, migration, invasion abilities, and enhanced the sensitivity to bicalutamide of PCa cells (P < 0.05 or P < 0.01 or P < 0.001). Downregulation of Wnt5a significantly inhibited miR-141-3p expression and promoter transcriptional activity (P < 0.01 or P < 0.05), whereas upregulation of Wnt5a significantly promoted miR-141-3p expression and promoter transcriptional activity (P < 0.01 or P < 0.001). The promoting effect of Wnt5a on miR-141-3p expression and promoter transcriptional activity could be inhibited by a JNK/c-Jun pathway inhibitor (P > 0.05). Downregulation of c-Jun significantly inhibited the promoting effect of Wnt5a on miR-141-3p expression and promoter transcriptional activity (P > 0.05). c-Jun could bind to the -348 to -295 sequence of the miR-141-3p promoter. In absence of this fragment Wnt5a wouldn’t promote miR-141-3p expression (P > 0.05). Conclusion: The Wnt5a/JNK/c-Jun signaling pathway can upregulate miR-141-3p expression, and thereby promote VM formation in PCa cells, possibly by activating CSC properties.
[Abstract] Objective: To investigate the effects of Wnt5a on the vasculogenic mimicry (VM) and cancer stem cell (CSC) properties of prostate cancer (PCa) cells by upregulating the expression of miR-141-3p. Methods: Human prostate epithelial cell line RWPE-1 and PCa cell lines PC-3, LNCaP, and DU145 were cultured. qPCR was employed to detect miR-141-3p expression, and Western blotting (WB) was used to measure Wnt5a protein levels. Stable Wnt5a-knockdown or miR-141-3p-knockdown LNCaP and DU145 cell lines were established respectively via plasmid transfection. VM formation ability was assessed by three-dimensional culture assay. Cell proliferation ability and drug sensitivity were measured by CCK-8 assay. Cell migration and invasion abilities were detected using wound healing and Transwell assays, respectively. The expressions of VM-related molecules and CSC markers were detected by qPCR and WB. Colony formation ability was determined by clonogenic assay. The proportion of CD133+ cells was sorted and calculated by flow cytometry. The expressions of miR-141-3p and Wnt5a in CD133+ and CD133– cells were detected by qPCR and WB. Stable Wnt5a-overexpressing PCa cell lines were constructed via plasmid transfection. The effects of Wnt5a and different Wnt pathway downstream inhibitors on miR-141-3p expression and promoter activity were detected by qPCR and dual-luciferase reporter assays. Expression of c-Jun was knocked down in Wnt5a-overexpressing cells using si-c-Jun transfection. The target binding relationship between c-Jun and the miR-141-3p promoter was verified by qPCR, dual-luciferase reporter assay, and chromatin immunoprecipitation assay. Results: The expressions of miR-141-3p and Wnt5a were significantly higher in PCa cells compared with those in RWPE-1 cells, with the highest relative expression in DU145 cells and the lowest in LNCaP cells (P < 0.001). Downregulation of Wnt5a or miR-141-3p significantly inhibited VM formation ability and stemness of PCa cells, and significantly suppressed the proliferation, migration, invasion abilities, and enhanced the sensitivity to bicalutamide of PCa cells (P < 0.05 or P < 0.01 or P < 0.001). Downregulation of Wnt5a significantly inhibited miR-141-3p expression and promoter transcriptional activity (P < 0.01 or P < 0.05), whereas upregulation of Wnt5a significantly promoted miR-141-3p expression and promoter transcriptional activity (P < 0.01 or P < 0.001). The promoting effect of Wnt5a on miR-141-3p expression and promoter transcriptional activity could be inhibited by a JNK/c-Jun pathway inhibitor (P > 0.05). Downregulation of c-Jun significantly inhibited the promoting effect of Wnt5a on miR-141-3p expression and promoter transcriptional activity (P > 0.05). c-Jun could bind to the -348 to -295 sequence of the miR-141-3p promoter. In absence of this fragment Wnt5a wouldn’t promote miR-141-3p expression (P > 0.05). Conclusion: The Wnt5a/JNK/c-Jun signaling pathway can upregulate miR-141-3p expression, and thereby promote VM formation in PCa cells, possibly by activating CSC properties.
3 HMMR promotes the progression of 4NQO-induced esophageal squamous cell carcinoma by mediating FAM83D
2025, 32(10):1019-1026.
DOI: 10.3872/j.issn.1007-385X.2025.10.003
Abstract:
[Abstract] Objective: To investigate the role of hyaluronic acid-mediated motion receptor (HMMR) in the malignant progression of esophageal squamous cell carcinoma (ESCC) cells and its potential molecular mechanisms. Methods: 8 samples of ESCC tissues and adjacent paracancerous tissues surgically removed at the Fourth Hospital of Hebei Medical University between January 2018 and December 2020, as well as ESCC cells KYSE-30 and KYSE-150, were collected. Western blotting (WB) and immunohistochemistry (IHC) were used to detect the expression of HMMR in ESCC tissues. RNA interference was used to knock down HMMR expression in KYSE-30 and KYSE-150 cells, and qPCR and WB were used to detect the knockdown effect. The effects of HMMR knockdown on the proliferation and invasion abilities of ESCC cells were detected by CCK-8 assay and Transwell assay, respectively. 4-nitroquinoline 1-oxide (4NQO) was used to induce carcinogenesis in mice and establish an ESCC model . H-E staining was used to observe the morphological changes of esophagus, and IHC was used to analyze the expressions of HMMR, FAM83D (family with sequence similarity 83 member D), E-cadherin and N-cadherin in tissues of different degrees of carcinogenesis in mice. Results: The expression level of HMMR in human ESCC tissues was significantly higher than that in adjacent paracancerous tissues (all P < 0.05). After HMMR knockdown, the proliferation and invasion abilities of KYSE-30 and KYSE-150 cells were significantly reduced (P < 0.05 or P < 0.01), and the expression level of FAM83D also decreased (all P < 0.01). In nude mouse tumor experiment, the body weight of mice in the 4NQO group was lower than that of the control group (all P < 0.05). The results of IHC staining showed that HMMR was highly expressed in tumor tissues (P < 0.05), and the expression of HMMR in high-grade intraepithelial neoplasia (HGIN) tissues was significantly higher than that in low-grade intraepithelial neoplasia (LGIN) tissues (P < 0.001). HMMR was positively correlated with the expressions of FAM83D and N-cadherin (r = 0.724, 0.870, all P < 0.001), and negatively correlated with the expression of E-cadherin (r = -0.714, P < 0.001). Conclusion: HMMR is highly expressed in ESCC tissues and may promote the progression of ESCC by up-regulating FAM83D expression.
[Abstract] Objective: To investigate the role of hyaluronic acid-mediated motion receptor (HMMR) in the malignant progression of esophageal squamous cell carcinoma (ESCC) cells and its potential molecular mechanisms. Methods: 8 samples of ESCC tissues and adjacent paracancerous tissues surgically removed at the Fourth Hospital of Hebei Medical University between January 2018 and December 2020, as well as ESCC cells KYSE-30 and KYSE-150, were collected. Western blotting (WB) and immunohistochemistry (IHC) were used to detect the expression of HMMR in ESCC tissues. RNA interference was used to knock down HMMR expression in KYSE-30 and KYSE-150 cells, and qPCR and WB were used to detect the knockdown effect. The effects of HMMR knockdown on the proliferation and invasion abilities of ESCC cells were detected by CCK-8 assay and Transwell assay, respectively. 4-nitroquinoline 1-oxide (4NQO) was used to induce carcinogenesis in mice and establish an ESCC model . H-E staining was used to observe the morphological changes of esophagus, and IHC was used to analyze the expressions of HMMR, FAM83D (family with sequence similarity 83 member D), E-cadherin and N-cadherin in tissues of different degrees of carcinogenesis in mice. Results: The expression level of HMMR in human ESCC tissues was significantly higher than that in adjacent paracancerous tissues (all P < 0.05). After HMMR knockdown, the proliferation and invasion abilities of KYSE-30 and KYSE-150 cells were significantly reduced (P < 0.05 or P < 0.01), and the expression level of FAM83D also decreased (all P < 0.01). In nude mouse tumor experiment, the body weight of mice in the 4NQO group was lower than that of the control group (all P < 0.05). The results of IHC staining showed that HMMR was highly expressed in tumor tissues (P < 0.05), and the expression of HMMR in high-grade intraepithelial neoplasia (HGIN) tissues was significantly higher than that in low-grade intraepithelial neoplasia (LGIN) tissues (P < 0.001). HMMR was positively correlated with the expressions of FAM83D and N-cadherin (r = 0.724, 0.870, all P < 0.001), and negatively correlated with the expression of E-cadherin (r = -0.714, P < 0.001). Conclusion: HMMR is highly expressed in ESCC tissues and may promote the progression of ESCC by up-regulating FAM83D expression.
2025, 32(10):1027-1035.
DOI: 10.3872/j.issn.1007-385X.2025.10.004
Abstract:
[Abstract] Objective: To explore the effects of granzyme M (GZMM) on the proliferation, invasion, migration, and angiogenesis of clear cell renal cell carcinoma (ccRCC) cells and the underlying molecular mechanisms. Methods: TCGA database and immunohistochemistry were used to analyze the expression of GZMM in ccRCC tissues and its correlation with clinicopathological features. CCK-8, Transwell, wound healing, and angiogenesis assays were used to detect the effects of GZMM on the proliferation, invasion, migration, and angiogenesis of ccRCC cells. Weston blot assay was employed to detect the effects of GZMM on the VEGF/ ERK signaling pathway. Results: TCGA database and immunohistochemical analysis showed that the expression of GZMM in ccRCC tissues was elevated (P < 0.01), and was correlated with Fuhrman grading and lymph node metastasis (both P < 0.05). Patients with high expression of GZMM had a poor prognosis (P < 0.05), and it was associated with FcerⅠ-mediated MAPK activation (P < 0.001). In ccRCC cells, knockdown of GZMM decreased the proliferation, invasion and migration abilities and inhibited ERK signaling pathway (both P < 0.05) while overexpression of GZMM promoted the proliferation, invasion and migration abilities and activated ERK signaling pathway (both P < 0.01). In HUVECs, secreted GZMM promoted the proliferation, migration, tubule formation and angiogenesis abilities of HUVECs and activated VEGF/ERK signaling pathway (both P < 0.05). Furthermore, U0126 inhibited the expressions of p-ERK, MMP2, and MMP9 (all P < 0.05), but did not affect the expressions of VEGFA and VEGFR2. Conclusion: The expression of GZMM was elevated in ccRCC tissues and was correlated with its Fuhrman grading and lymph node metastasis. GZMM promoted the angiogenesis and invasion of ccRCC by activating VEGF/ERK signaling pathway.
[Abstract] Objective: To explore the effects of granzyme M (GZMM) on the proliferation, invasion, migration, and angiogenesis of clear cell renal cell carcinoma (ccRCC) cells and the underlying molecular mechanisms. Methods: TCGA database and immunohistochemistry were used to analyze the expression of GZMM in ccRCC tissues and its correlation with clinicopathological features. CCK-8, Transwell, wound healing, and angiogenesis assays were used to detect the effects of GZMM on the proliferation, invasion, migration, and angiogenesis of ccRCC cells. Weston blot assay was employed to detect the effects of GZMM on the VEGF/ ERK signaling pathway. Results: TCGA database and immunohistochemical analysis showed that the expression of GZMM in ccRCC tissues was elevated (P < 0.01), and was correlated with Fuhrman grading and lymph node metastasis (both P < 0.05). Patients with high expression of GZMM had a poor prognosis (P < 0.05), and it was associated with FcerⅠ-mediated MAPK activation (P < 0.001). In ccRCC cells, knockdown of GZMM decreased the proliferation, invasion and migration abilities and inhibited ERK signaling pathway (both P < 0.05) while overexpression of GZMM promoted the proliferation, invasion and migration abilities and activated ERK signaling pathway (both P < 0.01). In HUVECs, secreted GZMM promoted the proliferation, migration, tubule formation and angiogenesis abilities of HUVECs and activated VEGF/ERK signaling pathway (both P < 0.05). Furthermore, U0126 inhibited the expressions of p-ERK, MMP2, and MMP9 (all P < 0.05), but did not affect the expressions of VEGFA and VEGFR2. Conclusion: The expression of GZMM was elevated in ccRCC tissues and was correlated with its Fuhrman grading and lymph node metastasis. GZMM promoted the angiogenesis and invasion of ccRCC by activating VEGF/ERK signaling pathway.
2025, 32(10):1036-1043.
DOI: 10.3872/j.issn.1007-385X.2025.10.005
Abstract:
[Abstract] Objective: To investigate the effects of RNA binding protein 15 (RBM15) on the malignant biological behaviors of cervical cancer cells by regulating the Wnt/β-catenin pathway through ATPase family AAA-domain containing 3A (ATAD3A). Methods: TCGA database was used to analyze the expression level of RBM15 mRNA in cervical cancer tissues and its relationship with patient prognosis. 32 samples of cervical cancer tissues and adjacent para-cancerous tissues surgically removed in Ganzhou People's Hospital between January and October 2024, as well as cervical cancer cells HeLa, MS-751, C-33A, and SiHa, were collected. The expression levels of RBM15 in cervical cancer tissues and cells were detected by immunohistochemistry and WB assay. m6 A modification sites in ATAD3A mRNA were screened by the SRAMP online database. The interaction between RBM15 and ATAD3A mRNA were identified by RNA immunoprecipitation assay, RNA decay assay, and salvage assay. Knockdown or overexpression of RBM15 and ATAD3A in cervical cancer HeLa and SiHa cells were conducted by RNA interference and viral infection. The expressions of mRNA and protein were detected by qPCR and WB methods, while the proliferation, migration, and invasion abilities of cells in each group were assessed by CCK-8 method, scratch assay, and Transwell assay. Results: The positivity rates of RBM15 mRNA and protein in cervical cancer tissues were significantly higher than those in adjacent para-cancerous tissues (both P < 0.001). The protein expression levels of RBM15 in cervical cancer cell lines HeLa, MS-751, C-33A, and SiHa were significantly higher than those in normal cervical cell lines Ect1/E6E7 (all P < 0.001). The 5-year progression free survival rate of the RBM15 mRNA high expression group was lower than that of the low expression group (P < 0.001). Compared with that in adjacent para-cancerous tissues, the expression level of ATAD3A was significantly upregulated in cervical cancer tissues (P < 0.001). RBM15 mRNA was positively correlated with ATAD3A mRNA (r = 0.601, P < 0.05). There were highly reliable m6 A modification sites at position 501, 5 312, 12 137 in ATAD3A mRNA. Overexpression of RBM15 in HeLa and SiHa cells led to an increase in ATAD3A mRNA and protein expressions, while knockdown of RBM15 resulted in a decrease in ATAD3A mRNA and protein expression (all P < 0.001). RNA immunoprecipitation experiment showed that compared with the IgG group, ATAD3A mRNA was significantly enriched in the immunoprecipitation of RBM15 antibody (both P < 0.001). MeRIP-qPCR experiment showed that there was significant m6 A methylation enrichment at positions ATAD3A mRNA 501, 5 312 and 12 137 (all P < 0.001). RNA decay experiments showed that knocking down RBM15 in HeLa and SiHa cells could reduce the half-life and stability of ATAD3A mRNA (all P < 0.001). Knocking down the expression of RBM15 in HeLa and SiHa cells could significantly inhibit the proliferation, migration, and invasion of cancer cells and significantly reduce the expressions of Wnt/β-catenin pathway related proteins Wnt3, β-catenin, and vimentin, while overexpression of ATAD3A could completely reverse the above inhibiting effects (all P < 0.001). Conclusion: RBM15 can modify ATAD3A mRNA and regulate the Wnt/β-catenin pathway through m6 A, and thus promote the proliferation, migration and invasion of cervical cancer cells.
[Abstract] Objective: To investigate the effects of RNA binding protein 15 (RBM15) on the malignant biological behaviors of cervical cancer cells by regulating the Wnt/β-catenin pathway through ATPase family AAA-domain containing 3A (ATAD3A). Methods: TCGA database was used to analyze the expression level of RBM15 mRNA in cervical cancer tissues and its relationship with patient prognosis. 32 samples of cervical cancer tissues and adjacent para-cancerous tissues surgically removed in Ganzhou People's Hospital between January and October 2024, as well as cervical cancer cells HeLa, MS-751, C-33A, and SiHa, were collected. The expression levels of RBM15 in cervical cancer tissues and cells were detected by immunohistochemistry and WB assay. m6 A modification sites in ATAD3A mRNA were screened by the SRAMP online database. The interaction between RBM15 and ATAD3A mRNA were identified by RNA immunoprecipitation assay, RNA decay assay, and salvage assay. Knockdown or overexpression of RBM15 and ATAD3A in cervical cancer HeLa and SiHa cells were conducted by RNA interference and viral infection. The expressions of mRNA and protein were detected by qPCR and WB methods, while the proliferation, migration, and invasion abilities of cells in each group were assessed by CCK-8 method, scratch assay, and Transwell assay. Results: The positivity rates of RBM15 mRNA and protein in cervical cancer tissues were significantly higher than those in adjacent para-cancerous tissues (both P < 0.001). The protein expression levels of RBM15 in cervical cancer cell lines HeLa, MS-751, C-33A, and SiHa were significantly higher than those in normal cervical cell lines Ect1/E6E7 (all P < 0.001). The 5-year progression free survival rate of the RBM15 mRNA high expression group was lower than that of the low expression group (P < 0.001). Compared with that in adjacent para-cancerous tissues, the expression level of ATAD3A was significantly upregulated in cervical cancer tissues (P < 0.001). RBM15 mRNA was positively correlated with ATAD3A mRNA (r = 0.601, P < 0.05). There were highly reliable m6 A modification sites at position 501, 5 312, 12 137 in ATAD3A mRNA. Overexpression of RBM15 in HeLa and SiHa cells led to an increase in ATAD3A mRNA and protein expressions, while knockdown of RBM15 resulted in a decrease in ATAD3A mRNA and protein expression (all P < 0.001). RNA immunoprecipitation experiment showed that compared with the IgG group, ATAD3A mRNA was significantly enriched in the immunoprecipitation of RBM15 antibody (both P < 0.001). MeRIP-qPCR experiment showed that there was significant m6 A methylation enrichment at positions ATAD3A mRNA 501, 5 312 and 12 137 (all P < 0.001). RNA decay experiments showed that knocking down RBM15 in HeLa and SiHa cells could reduce the half-life and stability of ATAD3A mRNA (all P < 0.001). Knocking down the expression of RBM15 in HeLa and SiHa cells could significantly inhibit the proliferation, migration, and invasion of cancer cells and significantly reduce the expressions of Wnt/β-catenin pathway related proteins Wnt3, β-catenin, and vimentin, while overexpression of ATAD3A could completely reverse the above inhibiting effects (all P < 0.001). Conclusion: RBM15 can modify ATAD3A mRNA and regulate the Wnt/β-catenin pathway through m6 A, and thus promote the proliferation, migration and invasion of cervical cancer cells.
2025, 32(10):1044-1052.
DOI: 10.3872/j.issn.1007-385X.2025.10.006
Abstract:
[Abstract] Objective: To investigate the effects of miR-7-5p on the proliferation, apoptosis, and immune escape of esophageal squamous cell carcinoma (ESCC) KYSE-150 cells by regulating forkhead box M1 (FOXM1). Methods: The targeted binding sites of miR-7-5p and FOXM1 were verified by the dual-luciferase reporter gene assay. The cancer tissues and adjacent paracancerous tissues as well as the basic clinical data of 56 ESCC patients hospitalized at Changzhou Geriatric Disease Hospital affiliated to Soochow University between January 2022 and October 2024 were collected. qRT-PCR was used to detect the expression levels of miR-7-5p and FOXM1 in ESCC tissues, and analyze the relationship between their expressions and clinicopathological characteristics. Normal cultured KYSE-150 cells were selected as the Control group Plasmids were transfected into KYSE-150 cells using Lipofectamine 3000 transfection reagent, and the cells were assigned into the Mimic-NC group, the miR-7-5p mimic group, the miR-7-5p mimic + OE-NC group, and the miR-7-5p mimic + OE-FOXM1 group. EdU staining and CCK-8 assay were used to detect the proliferation ability of KYSE-150 cells. Flow cytometry was performed to detect the apoptosis of KYSE-150 cells and CD8+ T cells. Western blot assay was performed to detect the expression levels of PD-L1, FOXM1, BAX, and PCNA proteins in KYSE-150 cells. A nude mouse transplanted tumor model of KYSE-150 cells was established to observe the effects of miR-7-5p overexpression on the growth of the transplanted tumors and the expressions of Ki-67 and FOXM1 in the tissues. Results: miR-7-5p could target and negatively regulate FOXM1 (P < 0.05). miR-7-5p expression was low and FOXM1 expression was high in ESCC tissues (both P < 0.05). The expressions of miR-7-5p and FOXM1 were significantly correlated with TNM stage and differentiation degree, respectively (all P < 0.05). The rates of EdUpositive cells, cell proliferation ability, CD8+ T cell apoptosis rate, as well as PD-L1, PCNA, and FOXM1 mRNA and protein in the miR-7-5p overexpression group were significantly reduced (all P < 0.05), while the apoptosis rate, miR-7-5p, and BAX increased significantly (all P < 0.05). Meanwhile, overexpression of FOXM1 could reverse the above effects (all P < 0.05). Overexpression of miR-7-5p decreased the mass and volume of transplanted tumors, and the expressions of Ki-67 and FOXM1 proteins in transplanted tumor tissues (all P < 0.05). Conclusion: Overexpression of miR-7-5p can significantly inhibit the proliferation and immune escape of KYSE-150 cells and promote cell apoptosis, which may be achieved by targeted negative regulation of FOXM1.
[Abstract] Objective: To investigate the effects of miR-7-5p on the proliferation, apoptosis, and immune escape of esophageal squamous cell carcinoma (ESCC) KYSE-150 cells by regulating forkhead box M1 (FOXM1). Methods: The targeted binding sites of miR-7-5p and FOXM1 were verified by the dual-luciferase reporter gene assay. The cancer tissues and adjacent paracancerous tissues as well as the basic clinical data of 56 ESCC patients hospitalized at Changzhou Geriatric Disease Hospital affiliated to Soochow University between January 2022 and October 2024 were collected. qRT-PCR was used to detect the expression levels of miR-7-5p and FOXM1 in ESCC tissues, and analyze the relationship between their expressions and clinicopathological characteristics. Normal cultured KYSE-150 cells were selected as the Control group Plasmids were transfected into KYSE-150 cells using Lipofectamine 3000 transfection reagent, and the cells were assigned into the Mimic-NC group, the miR-7-5p mimic group, the miR-7-5p mimic + OE-NC group, and the miR-7-5p mimic + OE-FOXM1 group. EdU staining and CCK-8 assay were used to detect the proliferation ability of KYSE-150 cells. Flow cytometry was performed to detect the apoptosis of KYSE-150 cells and CD8+ T cells. Western blot assay was performed to detect the expression levels of PD-L1, FOXM1, BAX, and PCNA proteins in KYSE-150 cells. A nude mouse transplanted tumor model of KYSE-150 cells was established to observe the effects of miR-7-5p overexpression on the growth of the transplanted tumors and the expressions of Ki-67 and FOXM1 in the tissues. Results: miR-7-5p could target and negatively regulate FOXM1 (P < 0.05). miR-7-5p expression was low and FOXM1 expression was high in ESCC tissues (both P < 0.05). The expressions of miR-7-5p and FOXM1 were significantly correlated with TNM stage and differentiation degree, respectively (all P < 0.05). The rates of EdUpositive cells, cell proliferation ability, CD8+ T cell apoptosis rate, as well as PD-L1, PCNA, and FOXM1 mRNA and protein in the miR-7-5p overexpression group were significantly reduced (all P < 0.05), while the apoptosis rate, miR-7-5p, and BAX increased significantly (all P < 0.05). Meanwhile, overexpression of FOXM1 could reverse the above effects (all P < 0.05). Overexpression of miR-7-5p decreased the mass and volume of transplanted tumors, and the expressions of Ki-67 and FOXM1 proteins in transplanted tumor tissues (all P < 0.05). Conclusion: Overexpression of miR-7-5p can significantly inhibit the proliferation and immune escape of KYSE-150 cells and promote cell apoptosis, which may be achieved by targeted negative regulation of FOXM1.
2025, 32(10):1053-1059.
DOI: 10.3872/j.issn.1007-385X.2025.10.007
Abstract:
[Abstract] Objective: To investigate the effects of phillyrin (PHN) on the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of glioma U251 cells by adjusting the high mobility group protein B1 (HMGB1)/receptor of advanced glycation endproduct (RAGE) signaling pathway. Methods: Human glioma U251cells were assigned into the PHN-0 group (treated with 0 μmol/L PHN), the low, medium, and high-dose PHN groups (PHN-50、PHN-100、PHN-200 groups, treated with 50, 100, and 200 μmol/L PHN respectively), the PHN + pcDNA-NC group (treated with 200 μmol/L PHN after transfection of pcDNA-NC plasmid), and the PHN + HMGB1 group (treated with 200 μmol/L PHN after transfection of overexpressed HMGB1 plasmid). The proliferation ability of cells in each group was detected by the CCK-8 method and the clone formation assay. The apoptosis level of cells in each group was detected by flow cytometry. The migration and invasion abilities of cells in each group were detected by the Transwell assay. ELISA was used to detect the IL-8 secretion level of cells in each group. Immunofluorescence was used to detect the positive rates of N-cadherin and E-cadherin in cells of each group. WB assay was performed to detect the expression levels of Toll like receptor 4 (TLR4), nuclear factor-kappa B (NF- κB), HMGB1, RAGE, N-cadherin, E-cadherin, cell cycle protein D1 (cyclin D1), cyclin dependent kinase 2 (CDK2), B-lymphoblastoma-2 (Bcl-2), Bcl-2 associated X protein (BAX) proteins in cells of each group. Results: Compared with those in the PHN-0 group, the proliferation activity, the number of clone formation, the numbers of invasion and migration, IL-8 secretion levels, the positive rate and protein expression of N-cadherin, and the expressions of TLR4, NF-κB, HMGB1, RAGE, cyclin D1 and CDK2 protein in the PHN-50, PHN-100, and PHN-200 groups decreased significantly (all P < 0.05); and the apoptosis rate, the positivity rate and protein expression of E-cadherin , and the BAX/Bcl-2 ratio increased significantly (all P < 0.05). At the same time, overexpression of HMGB1 could reverse the inhibitory effects of PHN on the proliferation, migration, invasion and EMT of U251 cells, as well as its promoting effect on the apoptosis (all P < 0.05). Conclusion: PHN inhibits the proliferation, invasion and EMT progression of glioma U251 cells through the HMGB1/RAGE signaling pathway.
[Abstract] Objective: To investigate the effects of phillyrin (PHN) on the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of glioma U251 cells by adjusting the high mobility group protein B1 (HMGB1)/receptor of advanced glycation endproduct (RAGE) signaling pathway. Methods: Human glioma U251cells were assigned into the PHN-0 group (treated with 0 μmol/L PHN), the low, medium, and high-dose PHN groups (PHN-50、PHN-100、PHN-200 groups, treated with 50, 100, and 200 μmol/L PHN respectively), the PHN + pcDNA-NC group (treated with 200 μmol/L PHN after transfection of pcDNA-NC plasmid), and the PHN + HMGB1 group (treated with 200 μmol/L PHN after transfection of overexpressed HMGB1 plasmid). The proliferation ability of cells in each group was detected by the CCK-8 method and the clone formation assay. The apoptosis level of cells in each group was detected by flow cytometry. The migration and invasion abilities of cells in each group were detected by the Transwell assay. ELISA was used to detect the IL-8 secretion level of cells in each group. Immunofluorescence was used to detect the positive rates of N-cadherin and E-cadherin in cells of each group. WB assay was performed to detect the expression levels of Toll like receptor 4 (TLR4), nuclear factor-kappa B (NF- κB), HMGB1, RAGE, N-cadherin, E-cadherin, cell cycle protein D1 (cyclin D1), cyclin dependent kinase 2 (CDK2), B-lymphoblastoma-2 (Bcl-2), Bcl-2 associated X protein (BAX) proteins in cells of each group. Results: Compared with those in the PHN-0 group, the proliferation activity, the number of clone formation, the numbers of invasion and migration, IL-8 secretion levels, the positive rate and protein expression of N-cadherin, and the expressions of TLR4, NF-κB, HMGB1, RAGE, cyclin D1 and CDK2 protein in the PHN-50, PHN-100, and PHN-200 groups decreased significantly (all P < 0.05); and the apoptosis rate, the positivity rate and protein expression of E-cadherin , and the BAX/Bcl-2 ratio increased significantly (all P < 0.05). At the same time, overexpression of HMGB1 could reverse the inhibitory effects of PHN on the proliferation, migration, invasion and EMT of U251 cells, as well as its promoting effect on the apoptosis (all P < 0.05). Conclusion: PHN inhibits the proliferation, invasion and EMT progression of glioma U251 cells through the HMGB1/RAGE signaling pathway.
2025, 32(10):1060-1064.
DOI: 10.3872/j.issn.1007-385X.2025.10.008
Abstract:
[Abstract] Objective: To investigate the effects of germacrone (GM) regulation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway on the proliferation, migration, invasion and apoptosis of prostate cancer (PCa) cells. Methods: PCa PC3 cells were randomly separated into the control group (normal culture), the L-GM, the M-GM, the H-GM groups (each treated with 120, 240, 480 μmol/L GM respectively), and the GM + RU.521 group (treated with 480 μmol/L GM + 1 μmol/L cGAS inhibitor RU.521). EdU staining, CCK-8 assay, scratch assay, Transwell assay, and flow cytometry were applied to detect the effects of GM on the proliferation, migration, invasion, and apoptosis of PC3 cells, respectively. WB assay was used to detect the effects of GM on the expressions of cGAS and STING proteins in PC3 cells. Results: Compared with those in the control group, the rate of EdU-positive cells, cell proliferation activity, scratch healing rate, and the number of invasive cells in the L-GM, M-GM, and H-GM groups were significantly reduced (all P < 0.05); the apoptosis rate increased (P < 0.05); the expressions of cGAS and STING proteins were significantly upregulated, and were concentration-dependent (all P < 0.05). Compared with those in the H-GM group, the rate of EdU positive cells, cell proliferation activity, scratch healing rate and the number of invasive cells in the GM + RU.521 group were significantly elevated (all P < 0.05); the cell apoptosis rate decreased (P < 0.05); and the expressions of cGAS and STING proteins were significantly downregulated (all P < 0.05). Conclusion: GM inhibits the proliferation, migration, invasion and promotes the apoptosis of PCa cells by activating the cGAS-STING signaling pathway.
[Abstract] Objective: To investigate the effects of germacrone (GM) regulation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway on the proliferation, migration, invasion and apoptosis of prostate cancer (PCa) cells. Methods: PCa PC3 cells were randomly separated into the control group (normal culture), the L-GM, the M-GM, the H-GM groups (each treated with 120, 240, 480 μmol/L GM respectively), and the GM + RU.521 group (treated with 480 μmol/L GM + 1 μmol/L cGAS inhibitor RU.521). EdU staining, CCK-8 assay, scratch assay, Transwell assay, and flow cytometry were applied to detect the effects of GM on the proliferation, migration, invasion, and apoptosis of PC3 cells, respectively. WB assay was used to detect the effects of GM on the expressions of cGAS and STING proteins in PC3 cells. Results: Compared with those in the control group, the rate of EdU-positive cells, cell proliferation activity, scratch healing rate, and the number of invasive cells in the L-GM, M-GM, and H-GM groups were significantly reduced (all P < 0.05); the apoptosis rate increased (P < 0.05); the expressions of cGAS and STING proteins were significantly upregulated, and were concentration-dependent (all P < 0.05). Compared with those in the H-GM group, the rate of EdU positive cells, cell proliferation activity, scratch healing rate and the number of invasive cells in the GM + RU.521 group were significantly elevated (all P < 0.05); the cell apoptosis rate decreased (P < 0.05); and the expressions of cGAS and STING proteins were significantly downregulated (all P < 0.05). Conclusion: GM inhibits the proliferation, migration, invasion and promotes the apoptosis of PCa cells by activating the cGAS-STING signaling pathway.
XU Fan
,
TIAN Jianhui
,
LIU Youjun
,
CHENG Zhenyang
,
QUE Zuju
,
LUO Bin
,
YANG Yun
,
YAO Jialiang
,
YAO Wang
,
LU Xinyi
,
LIU Yao
,
ZHOU Yiyang
,
WU Jianchun
,
LUO Yingbin
,
LI Minghua
,
SHI Wenfei
,
CUI Yajing
,
SHANGGUAN Wenji
,
LI Yan
2025, 32(10):1065-1070.
DOI: 10.3872/j.issn.1007-385X.2025.10.009
Abstract:
[Abstract] Objective: To investigate the association between peripheral immune function status and lung cancer metastasis, and to identify peripheral blood immune biomarkers for ‘Deficiency of Vital Qi’assessment in lung cancer metastasis. Methods: A retrospective analysis was conducted on peripheral blood immune markers collected before treatment from lung cancer patients admitted into Shanghai Municipal Hospital of Traditional Chinese Medicine, affiliated to Shanghai University of Traditional Chinese Medicine, between March 2023 and April 2025. Patients were categorized into the non-metastatic and the metastatic groups based on the presence of distant metastasis, and the differences in the expressions of immune cells and cytokines between groups were compared. Peripheral blood immune markers with P < 0.05 in univariate analysis were incorporated into a multivariate binary logistic regression model to identify independent predictors of lung cancer metastasis. Results: A total of 193 lung cancer patients were included (101 in the non-metastatic group and 92 in the metastatic group). There were no statistically significant differences between the two groups in terms of gender, age, smoking history, drinking history, or pathological type (all P > 0.05). Univariate analysis revealed significant differences in multiple immune markers between the non-metastatic and metastatic groups (all P < 0.05), including: lymphocyte count, CD3+, CD4+, and CD8+ T, CD19+ B cells, absolute counts of CD3-CD16+CD56+ NK cells, percentages of Treg cells, CD8+CD28+ Treg cells, G-MDSC, and CD3-CD16+CD56+dim NK cells , and levels of cytokine IL-1β, IL-6, and IL-10. Binary logistic regression analysis of differential indicators suggested that the percentage of Treg cells and CD8+CD28+ Treg cells in peripheral blood were independent predictors of distant metastasis in lung cancer (OR = 1.193, 95% CI [1.047, 1.36], P < 0.01; OR = 0.978, 95% CI [0.957, 0.999], P < 0.05). Conclusion: Peripheral blood immune dysfunction is the biological basis for 'qi deficiency' in lung cancer metastasis. This study quantitatively demonstrates the correlation between peripheral immune function status and lung cancer metastasis, providing empirical evidence for the theories of 'qi deficiency and hidden toxicity' and 'metastatic state of tumors'.
[Abstract] Objective: To investigate the association between peripheral immune function status and lung cancer metastasis, and to identify peripheral blood immune biomarkers for ‘Deficiency of Vital Qi’assessment in lung cancer metastasis. Methods: A retrospective analysis was conducted on peripheral blood immune markers collected before treatment from lung cancer patients admitted into Shanghai Municipal Hospital of Traditional Chinese Medicine, affiliated to Shanghai University of Traditional Chinese Medicine, between March 2023 and April 2025. Patients were categorized into the non-metastatic and the metastatic groups based on the presence of distant metastasis, and the differences in the expressions of immune cells and cytokines between groups were compared. Peripheral blood immune markers with P < 0.05 in univariate analysis were incorporated into a multivariate binary logistic regression model to identify independent predictors of lung cancer metastasis. Results: A total of 193 lung cancer patients were included (101 in the non-metastatic group and 92 in the metastatic group). There were no statistically significant differences between the two groups in terms of gender, age, smoking history, drinking history, or pathological type (all P > 0.05). Univariate analysis revealed significant differences in multiple immune markers between the non-metastatic and metastatic groups (all P < 0.05), including: lymphocyte count, CD3+, CD4+, and CD8+ T, CD19+ B cells, absolute counts of CD3-CD16+CD56+ NK cells, percentages of Treg cells, CD8+CD28+ Treg cells, G-MDSC, and CD3-CD16+CD56+dim NK cells , and levels of cytokine IL-1β, IL-6, and IL-10. Binary logistic regression analysis of differential indicators suggested that the percentage of Treg cells and CD8+CD28+ Treg cells in peripheral blood were independent predictors of distant metastasis in lung cancer (OR = 1.193, 95% CI [1.047, 1.36], P < 0.01; OR = 0.978, 95% CI [0.957, 0.999], P < 0.05). Conclusion: Peripheral blood immune dysfunction is the biological basis for 'qi deficiency' in lung cancer metastasis. This study quantitatively demonstrates the correlation between peripheral immune function status and lung cancer metastasis, providing empirical evidence for the theories of 'qi deficiency and hidden toxicity' and 'metastatic state of tumors'.
2025, 32(10):1071-1077.
DOI: 10.3872/j.issn.1007-385X.2025.10.010
Abstract:
[Abstract] Objective: To investigate the clinical efficacy of histone deacetylase (HDAC) inhibitor chidamide combined with CHOP in the treatment of preliminarily diagnosed peripheral T-cell lymphoma (PTCL) and to analyze the factors influencing its prognosis. Methods: Clinical data were collected from patients who were preliminarily diagnosed with PTCL, but had not received radiotherapy or chemotherapy at the Affiliated Hospital of Nantong University between April 2012 and August 2022. The patients were divided into two groups, based on the frontline treatment regimen: the chidamide + CHOP group (n = 20) and the CHOP group (n = 24). The differences in clinicopathological characteristics between the two groups were compared by chi-square test or Fisher's exact test. Survival curves were generated by Kaplan-Meier method, and univariate survival analysis was conducted by Log-Rank test. Subgroup analysis was performed to assess the survival outcomes of patients in the chidamide + CHOP group, and interaction tests were conducted to assess the factors that might influence the difference in survival prognosis between the two groups. Results: The baseline levels of the two groups were comparable in age, gender, and tumor stage, but there were more AITL patients (70.8% vs 15%) and fewer PTCL-NOS patients (16.7% vs 30%) in the chidamide + CHOP group . Efficacy analysis revealed that the median PFS was significantly longer in patients treated with chidamide + CHOP (7 months vs 3 months, P = 0.032), and their median OS was also significantly longer (20 months vs 6 months, P = 0.004). Univariate prognostic analysis revealed that PTCL patients with B symptoms had significantly poorer PFS (P = 0.053) and OS (P = 0.065) than PTCL patients without B symptoms; and patients with elevated baseline LDH levels had a worse OS (P = 0.056). Further subgroup analysis of efficacy revealed that, among patients with normal baseline serum ferritin levels, those in the chidamide + CHOP group had significantly better PFS compared with those in the CHOP group (95% CI [1.14, 43.58]). The interaction test between serum ferritin levels and treatment regimens demonstrated statistical significance (P = 0.042). Conclusion: The combination of chidamide and CHOP has survival benefits for patients preliminarily diagnosed with PTCL, and baseline serum ferritin levels may serve as a potential predictor for combination therapy.
[Abstract] Objective: To investigate the clinical efficacy of histone deacetylase (HDAC) inhibitor chidamide combined with CHOP in the treatment of preliminarily diagnosed peripheral T-cell lymphoma (PTCL) and to analyze the factors influencing its prognosis. Methods: Clinical data were collected from patients who were preliminarily diagnosed with PTCL, but had not received radiotherapy or chemotherapy at the Affiliated Hospital of Nantong University between April 2012 and August 2022. The patients were divided into two groups, based on the frontline treatment regimen: the chidamide + CHOP group (n = 20) and the CHOP group (n = 24). The differences in clinicopathological characteristics between the two groups were compared by chi-square test or Fisher's exact test. Survival curves were generated by Kaplan-Meier method, and univariate survival analysis was conducted by Log-Rank test. Subgroup analysis was performed to assess the survival outcomes of patients in the chidamide + CHOP group, and interaction tests were conducted to assess the factors that might influence the difference in survival prognosis between the two groups. Results: The baseline levels of the two groups were comparable in age, gender, and tumor stage, but there were more AITL patients (70.8% vs 15%) and fewer PTCL-NOS patients (16.7% vs 30%) in the chidamide + CHOP group . Efficacy analysis revealed that the median PFS was significantly longer in patients treated with chidamide + CHOP (7 months vs 3 months, P = 0.032), and their median OS was also significantly longer (20 months vs 6 months, P = 0.004). Univariate prognostic analysis revealed that PTCL patients with B symptoms had significantly poorer PFS (P = 0.053) and OS (P = 0.065) than PTCL patients without B symptoms; and patients with elevated baseline LDH levels had a worse OS (P = 0.056). Further subgroup analysis of efficacy revealed that, among patients with normal baseline serum ferritin levels, those in the chidamide + CHOP group had significantly better PFS compared with those in the CHOP group (95% CI [1.14, 43.58]). The interaction test between serum ferritin levels and treatment regimens demonstrated statistical significance (P = 0.042). Conclusion: The combination of chidamide and CHOP has survival benefits for patients preliminarily diagnosed with PTCL, and baseline serum ferritin levels may serve as a potential predictor for combination therapy.
2025, 32(10):1078-1083.
DOI: 10.3872/j.issn.1007-385X.2025.10.011
Abstract:
[摘 要] 组蛋白乳酸化作为一种新型的组蛋白翻译后修饰，通过乳酸与组蛋白赖氨酸残基的共价结合，紧密联系细胞代谢与 基因表达调控。研究发现，乳酸化修饰在肿瘤增殖、免疫逃逸、微环境重塑及治疗耐药中发挥关键作用。组蛋白乳酸化修饰通过 调控关键基因和细胞信号通路的表达，促进肿瘤细胞的增殖和迁移；通过影响免疫逃逸相关基因和免疫检查点分子的表达、重塑 肿瘤微环境（TME）抑制免疫细胞功能，帮助肿瘤细胞逃避免疫系统的监视，进一步促进肿瘤的生长和进展；通过调节代谢重编程 和信号通路，增强肿瘤细胞对治疗的耐药性。因此，基于乳酸化修饰的分子机制、肿瘤生物学功能及其在生物治疗中的应用潜 力，靶向组蛋白乳酸化修饰的肿瘤诊断与治疗新策略的重要性不言而喻。
[摘 要] 组蛋白乳酸化作为一种新型的组蛋白翻译后修饰，通过乳酸与组蛋白赖氨酸残基的共价结合，紧密联系细胞代谢与 基因表达调控。研究发现，乳酸化修饰在肿瘤增殖、免疫逃逸、微环境重塑及治疗耐药中发挥关键作用。组蛋白乳酸化修饰通过 调控关键基因和细胞信号通路的表达，促进肿瘤细胞的增殖和迁移；通过影响免疫逃逸相关基因和免疫检查点分子的表达、重塑 肿瘤微环境（TME）抑制免疫细胞功能，帮助肿瘤细胞逃避免疫系统的监视，进一步促进肿瘤的生长和进展；通过调节代谢重编程 和信号通路，增强肿瘤细胞对治疗的耐药性。因此，基于乳酸化修饰的分子机制、肿瘤生物学功能及其在生物治疗中的应用潜 力，靶向组蛋白乳酸化修饰的肿瘤诊断与治疗新策略的重要性不言而喻。
2025, 32(10):1084-1089.
DOI: 10.3872/j.issn.1007-385X.2025.10.012
Abstract:
[摘 要] 肿瘤内微生物由细菌、真菌、病毒和支原体组成，主要分布于肿瘤细胞与多种免疫细胞中。研究已证实，几乎所有实 体瘤均存在肿瘤内微生物，其分布具有肿瘤类型依赖性。肿瘤内微生物通过调节肿瘤微环境（TME），促进或抑制肿瘤的生长与进 展。这些微生物不仅能够影响TME的免疫状态，还可作为预测免疫治疗疗效的新型生物标志物。本文首先综述肿瘤内微生物的 来源及其在各类肿瘤中的作用，聚焦结直肠癌、肝癌和胃癌中肿瘤内微生物的组成及其在肿瘤进展中的作用机制；最后，深入探 讨肿瘤内微生物在调节肿瘤免疫微环境中的意义，评估其在免疫治疗中的潜在价值，揭示肿瘤内微生物靶向疗法与免疫治疗相 结合的前景，为肿瘤的精准治疗提供新的理论依据。
[摘 要] 肿瘤内微生物由细菌、真菌、病毒和支原体组成，主要分布于肿瘤细胞与多种免疫细胞中。研究已证实，几乎所有实 体瘤均存在肿瘤内微生物，其分布具有肿瘤类型依赖性。肿瘤内微生物通过调节肿瘤微环境（TME），促进或抑制肿瘤的生长与进 展。这些微生物不仅能够影响TME的免疫状态，还可作为预测免疫治疗疗效的新型生物标志物。本文首先综述肿瘤内微生物的 来源及其在各类肿瘤中的作用，聚焦结直肠癌、肝癌和胃癌中肿瘤内微生物的组成及其在肿瘤进展中的作用机制；最后，深入探 讨肿瘤内微生物在调节肿瘤免疫微环境中的意义，评估其在免疫治疗中的潜在价值，揭示肿瘤内微生物靶向疗法与免疫治疗相 结合的前景，为肿瘤的精准治疗提供新的理论依据。
2025, 32(10):1090-1097.
DOI: 10.3872/j.issn.1007-385X.2025.10.013
Abstract:
[摘 要] 白细胞介素-15（IL-15）是4-α螺旋束细胞因子家族成员，主要由活化的单核细胞和树突状细胞（DC）分泌等，可通过调控NK细胞和T 细胞的发育、稳态及功能，目前已经成为肿瘤免疫治疗的研究热点。然而，由于IL-15的靶向性不足、体内半衰期短及潜在的毒性作用等限制了其 在实体瘤免疫治疗中的广泛应用。本文聚焦IL-15激动剂的结构改造与功能优化，重点剖析其在实体瘤治疗中进行的靶向性优化、长循环及多功 能设计等改造策略，总结其在临床研究中与免疫检查点抑制剂（ICI）、过继细胞疗法等联合应用的最新研究进展，为推动IL-15激动剂的临床转化 提供了新的思路与理论依据。
[摘 要] 白细胞介素-15（IL-15）是4-α螺旋束细胞因子家族成员，主要由活化的单核细胞和树突状细胞（DC）分泌等，可通过调控NK细胞和T 细胞的发育、稳态及功能，目前已经成为肿瘤免疫治疗的研究热点。然而，由于IL-15的靶向性不足、体内半衰期短及潜在的毒性作用等限制了其 在实体瘤免疫治疗中的广泛应用。本文聚焦IL-15激动剂的结构改造与功能优化，重点剖析其在实体瘤治疗中进行的靶向性优化、长循环及多功 能设计等改造策略，总结其在临床研究中与免疫检查点抑制剂（ICI）、过继细胞疗法等联合应用的最新研究进展，为推动IL-15激动剂的临床转化 提供了新的思路与理论依据。
2025, 32(10):1098-1100.
DOI: 10.3872/j.issn.1007-385X.2025.10.014
Abstract:
[摘 要] 胸腺鳞状细胞癌（TSCC）作为罕见的高度侵袭性肿瘤，其预后极差。TSCC患者中位总生存期（OS）不足1年，且缺乏 标准治疗方案。虽然，目前免疫联合抗血管靶向治疗为晚期TSCC患者带来新的治疗契机，但最佳方案尚未确立。本文报道1例 初诊Ⅳ期TSCC女性患者，先后接受DC-CIK、CDK4/6抑制剂、PD-1单抗、双特异性抗体等多线治疗后仍快速进展，并出现肝、骨 转移。2024年2月起改用信迪利单抗联合安罗替尼治疗，连续随访14个月，胸腺病灶持续缩小，肝、骨转移灶保持稳定，无进展生 存期（PFS）已逾14个月，OS达51个月，未见≥ 3级不良反应。结合文献回顾，该方案在PD-L1低表达且既往多线免疫治疗失败的 患者中仍能实现长期疾病控制，提示抗血管生成药物可能逆转免疫耐药。信迪利单抗联合安罗替尼或可作为后线晚期TSCC的 新选择，其一线应用价值值得进一步验证。
[摘 要] 胸腺鳞状细胞癌（TSCC）作为罕见的高度侵袭性肿瘤，其预后极差。TSCC患者中位总生存期（OS）不足1年，且缺乏 标准治疗方案。虽然，目前免疫联合抗血管靶向治疗为晚期TSCC患者带来新的治疗契机，但最佳方案尚未确立。本文报道1例 初诊Ⅳ期TSCC女性患者，先后接受DC-CIK、CDK4/6抑制剂、PD-1单抗、双特异性抗体等多线治疗后仍快速进展，并出现肝、骨 转移。2024年2月起改用信迪利单抗联合安罗替尼治疗，连续随访14个月，胸腺病灶持续缩小，肝、骨转移灶保持稳定，无进展生 存期（PFS）已逾14个月，OS达51个月，未见≥ 3级不良反应。结合文献回顾，该方案在PD-L1低表达且既往多线免疫治疗失败的 患者中仍能实现长期疾病控制，提示抗血管生成药物可能逆转免疫耐药。信迪利单抗联合安罗替尼或可作为后线晚期TSCC的 新选择，其一线应用价值值得进一步验证。
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
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.
Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.