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Volume 33,Issue 2,2026 Table of Contents
2026, 33(2):111-119.
DOI: 10.3872/j.issn.1007-385X.2026.02.001
Abstract:
[Abstract] The clinical benefits of tumor immunotherapy are still limited by non-responses or resistance of cancer patients. Tumortargeted replicating oncolytic viruses (TOV) can act as "initiators" and "catalysts" for immunotherapy, converting "cold" tumors into "hot" tumors, with controllable safety and good tolerance. This article systematically reviews the mechanism, clinical progress, and key challenges of TOV and possible solutions to overcome the challenges, focusing on discussing the impact of the host immune system on TOV, the development of more effective TOV platforms, strategies for efficient intravenous administration of TOV, the choice of preclinical animal evaluation models with better clinical predictive value, the optimization of treatment scheduling of combination therapy and directions for future development. This review discusses the potential of TOV as a pivotal synergistic and catalytic platform in cancer immunotherapy, proposing novel strategies to enhance immune responses and achieve long-term efficacy against solid tumors.
[Abstract] The clinical benefits of tumor immunotherapy are still limited by non-responses or resistance of cancer patients. Tumortargeted replicating oncolytic viruses (TOV) can act as "initiators" and "catalysts" for immunotherapy, converting "cold" tumors into "hot" tumors, with controllable safety and good tolerance. This article systematically reviews the mechanism, clinical progress, and key challenges of TOV and possible solutions to overcome the challenges, focusing on discussing the impact of the host immune system on TOV, the development of more effective TOV platforms, strategies for efficient intravenous administration of TOV, the choice of preclinical animal evaluation models with better clinical predictive value, the optimization of treatment scheduling of combination therapy and directions for future development. This review discusses the potential of TOV as a pivotal synergistic and catalytic platform in cancer immunotherapy, proposing novel strategies to enhance immune responses and achieve long-term efficacy against solid tumors.
2026, 33(2):120-131.
DOI: 10.3872/j.issn.1007-385X.2026.02.002
Abstract:
[Abstract] Objective: To develop a novel delivery system for oncolytic reovirus (Reo) to circumvent neutralization by anti-Reo antibodies and enhance tumor-targeting efficiency. Methods: Natural killer cell-derived exosomes (NKexo) were prepared via tangential flow filtration combined with ultracentrifugation. After folic acid (FA) modification, Reo was encapsulated into NKexo using an extrusion method to construct the FA-NKexo-Reo delivery system. The physicochemical properties of FA-NKexo-Reo were characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis, Western blot, proton nuclear magnetic resonance spectroscopy, and flow cytometry. The in vitro cytotoxicity and cellular uptake of FA-NKexo-Reo was evaluated using CCK-8 assays, flow cytometry, Transwell assays, and confocal laser microscopy. A human ovarian cancer xenograft model in nude mice was established to assess the tumor-targeting capability, therapeutic efficacy, and treatment safety of FA-NKexo-Reo. Results: FA-NKexoReo exhibited an average particle size of (94.0 ± 28.5) nm and a zeta potential of (?21.26 ± 1.57) mV, with an encapsulation efficiency of (49.7 ± 15.6)% . In the presence of neutralizing antibodies, FA-NKexo-Reo retained significant cytotoxicity against SKOV3 and A2780 ovarian cancer cells (P < 0.01). In vivo fluorescence imaging demonstrated superior tumor-targeting capability of FA-NKexo-Reo compared to NKexo, with a 60% increase in tumor suppression rate (P < 0.001). Conclusion: The FA-NKexo-Reo delivery system was successfully prepared. In the presence of neutralizing antibodies, FA-NKexo-Reo effectively protects and selectively delivers Reo to ovarian cancer cells with high folate receptor expression, significantly enhancing the antitumor efficacy of Reo.
[Abstract] Objective: To develop a novel delivery system for oncolytic reovirus (Reo) to circumvent neutralization by anti-Reo antibodies and enhance tumor-targeting efficiency. Methods: Natural killer cell-derived exosomes (NKexo) were prepared via tangential flow filtration combined with ultracentrifugation. After folic acid (FA) modification, Reo was encapsulated into NKexo using an extrusion method to construct the FA-NKexo-Reo delivery system. The physicochemical properties of FA-NKexo-Reo were characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis, Western blot, proton nuclear magnetic resonance spectroscopy, and flow cytometry. The in vitro cytotoxicity and cellular uptake of FA-NKexo-Reo was evaluated using CCK-8 assays, flow cytometry, Transwell assays, and confocal laser microscopy. A human ovarian cancer xenograft model in nude mice was established to assess the tumor-targeting capability, therapeutic efficacy, and treatment safety of FA-NKexo-Reo. Results: FA-NKexoReo exhibited an average particle size of (94.0 ± 28.5) nm and a zeta potential of (?21.26 ± 1.57) mV, with an encapsulation efficiency of (49.7 ± 15.6)% . In the presence of neutralizing antibodies, FA-NKexo-Reo retained significant cytotoxicity against SKOV3 and A2780 ovarian cancer cells (P < 0.01). In vivo fluorescence imaging demonstrated superior tumor-targeting capability of FA-NKexo-Reo compared to NKexo, with a 60% increase in tumor suppression rate (P < 0.001). Conclusion: The FA-NKexo-Reo delivery system was successfully prepared. In the presence of neutralizing antibodies, FA-NKexo-Reo effectively protects and selectively delivers Reo to ovarian cancer cells with high folate receptor expression, significantly enhancing the antitumor efficacy of Reo.
2026, 33(2):132-139.
DOI: 10.3872/j.issn.1007-385X.2026.02.003
Abstract:
[Abstract] Objective: To investigate the role and underlying mechanism of myxovirus resistance protein 2 (MX2), a member of the interferon-stimulated gene family, in modulating tumor cell sensitivity to reovirus (Reo)-mediated oncolysis. Methods: Four human tumor cell lines with distinct drug-resistance characteristics were selected, and their sensitivity to Reo-mediated oncolysis was evaluated using the CCK-8 assay. Transcriptome sequencing was performed to identify differentially expressed genes, and MX2 was screened as a candidate gene. The differential expression of MX2 was validated by qPCR and WB assay. In the Reo-low-sensitive COC1/DDP cells, MX2 was knocked down using siRNA, followed by Reo infection, and cell viability was assessed using CCK-8 assay. Viral replication was evaluated by measuring S1 gene expression using qPCR, intracellular viral protein accumulation by immunofluorescence staining, and viral titer by the TCID50 assay. Intracellular Reo dsRNA levels, reactive oxygen species (ROS) production, and apoptosis rates were measured using flow cytometry. Ultrastructural changes in the endoplasmic reticulum (ER) were examined using transmission electron microscopy (TEM). Additionally, WB was used to assess the expression of ER stress-related proteins, including JNK, p-JNK, eIF2α, p-eIF2α, CHOP, and PERK. Results: Among the four tested tumor cell lines, SKOV3 cells exhibited high sensitivity to Reo-mediated oncolysis, whereas COC1/DDP, HuH-7SRB , and SNU-398 cells showed low sensitivity. Transcriptome sequencing revealed that MX2 expression was significantly higher in Reo-low-sensitive cell lines compared with Reo-high-sensitive cells (P < 0.01). In COC1/DDP cells, MX2 knockdown markedly enhanced Reo replication, increased apoptosis, and elevated intracellular ROS levels (all P < 0.001). TEM revealed typical ultrastructural features of ER stress in MX2-knockdown COC1/DDP cells following Reo infection, including ER swelling, dilation, and fragmentation. WB analysis showed significant upregulation of key ER stress markers (p-eIF2α/eIF2α, PERK, and CHOP) and apoptosis-related regulatory proteins JNK/ p-JNK (P < 0.05 or P < 0.01). Conclusion: Tumor cell sensitivity to Reo-mediated oncolysis is closely associated with intracellular MX2 expression levels. Knockdown of MX2 significantly enhanced intracellular Reo replication, leading to ROS accumulation, activation of ER stress, and induction of apoptosis. The synergistic effects of enhanced viral replication and apoptosis ultimately potentiate the oncolytic efficacy of Reo.
[Abstract] Objective: To investigate the role and underlying mechanism of myxovirus resistance protein 2 (MX2), a member of the interferon-stimulated gene family, in modulating tumor cell sensitivity to reovirus (Reo)-mediated oncolysis. Methods: Four human tumor cell lines with distinct drug-resistance characteristics were selected, and their sensitivity to Reo-mediated oncolysis was evaluated using the CCK-8 assay. Transcriptome sequencing was performed to identify differentially expressed genes, and MX2 was screened as a candidate gene. The differential expression of MX2 was validated by qPCR and WB assay. In the Reo-low-sensitive COC1/DDP cells, MX2 was knocked down using siRNA, followed by Reo infection, and cell viability was assessed using CCK-8 assay. Viral replication was evaluated by measuring S1 gene expression using qPCR, intracellular viral protein accumulation by immunofluorescence staining, and viral titer by the TCID50 assay. Intracellular Reo dsRNA levels, reactive oxygen species (ROS) production, and apoptosis rates were measured using flow cytometry. Ultrastructural changes in the endoplasmic reticulum (ER) were examined using transmission electron microscopy (TEM). Additionally, WB was used to assess the expression of ER stress-related proteins, including JNK, p-JNK, eIF2α, p-eIF2α, CHOP, and PERK. Results: Among the four tested tumor cell lines, SKOV3 cells exhibited high sensitivity to Reo-mediated oncolysis, whereas COC1/DDP, HuH-7SRB , and SNU-398 cells showed low sensitivity. Transcriptome sequencing revealed that MX2 expression was significantly higher in Reo-low-sensitive cell lines compared with Reo-high-sensitive cells (P < 0.01). In COC1/DDP cells, MX2 knockdown markedly enhanced Reo replication, increased apoptosis, and elevated intracellular ROS levels (all P < 0.001). TEM revealed typical ultrastructural features of ER stress in MX2-knockdown COC1/DDP cells following Reo infection, including ER swelling, dilation, and fragmentation. WB analysis showed significant upregulation of key ER stress markers (p-eIF2α/eIF2α, PERK, and CHOP) and apoptosis-related regulatory proteins JNK/ p-JNK (P < 0.05 or P < 0.01). Conclusion: Tumor cell sensitivity to Reo-mediated oncolysis is closely associated with intracellular MX2 expression levels. Knockdown of MX2 significantly enhanced intracellular Reo replication, leading to ROS accumulation, activation of ER stress, and induction of apoptosis. The synergistic effects of enhanced viral replication and apoptosis ultimately potentiate the oncolytic efficacy of Reo.
2026, 33(2):140-146.
DOI: 10.3872/j.issn.1007-385X.2026.02.004
Abstract:
[Abstract] Objective: To establish a recombinant particle protein using hepatitis B core protein (HBc) virus-like particles (VLPs) as the scaffold, with chimeric incorporation of PD-1 B cell epitopes, and to investigate its inhibitory effect on colorectal cancer in mice. Methods: A PD-1 HBc VLPs plasmid was designed and introduced into Escherichia coli BL21 (DE3) to obtain recombinant PD-1 HBc VLPs-expressing strains. Soluble protein expression was achieved by optimizing the culture temperature. Subsequently, high-purity PD-1 HBc VLPs were obtained via a series of purification steps, including ammonium sulfate precipitation, size-exclusion chromatography, and anion-exchange chromatography. The expression level, protein purity, particle formation efficiency, morphological characteristics, and antigen-binding activity of the obtained PD-1 HBc VLPs were systematically characterized by electrophoresis, WB, highperformance liquid chromatography (HPLC), and transmission electron microscopy. Immunogenicity was evaluated by ELISA to determine serum antibody titers in immunized mice. CT26 colorectal carcinoma cell transplant tumor model was constructed in mice, and the anti-tumor activity of PD-1 HBc VLPs was further assessed in vivo by comparing tumor growth, body weight and tumor volume changes. Results: At 28 ℃, the soluble target protein accounted for 10.27% of total protein. The target protein was purified using Sepharose 4 Fast Flow molecular sieve and DEAE anion resin chromatography, with a purity of (91.77 ± 0.62)% and a molecular weight of 23 000. The particle size measured by electron microscopy was (31.90 ± 1.88) nm, while particle size analyzer showed a particle size of (30.66 ± 0.62) nm, and the polydispersity index (PDI) was (0.18 ± 0.05). WB analysis demonstrated that the recombinant PD-1 HBc VLPs could bind to anti-HBc VLPs serum and anti-PD-1 antibodies, respectively. ELISA results showed that on day 14 after the third immunization with PD-1 HBc VLPs, the total antibody titer in mouse serum reached 1∶640 000, with an anti-PD-1 antibody titer of 1∶40 000. Anti-tumor experiments showed that PD-1 HBc VLPs achieved a tumor inhibition rate of (27.99 ± 2.98)% in mice with colorectal carcinoma. All mice in the control group died by day 45, whereas the median survival time (MST) in the PD-1 HBc VLPs group was prolonged by 20 days. Conclusion: PD-1 HBc VLPs containing PD-1 B cell epitopes were successfully prepared and demonstrated therapeutic efficacy against colorectal cancer in mice.
[Abstract] Objective: To establish a recombinant particle protein using hepatitis B core protein (HBc) virus-like particles (VLPs) as the scaffold, with chimeric incorporation of PD-1 B cell epitopes, and to investigate its inhibitory effect on colorectal cancer in mice. Methods: A PD-1 HBc VLPs plasmid was designed and introduced into Escherichia coli BL21 (DE3) to obtain recombinant PD-1 HBc VLPs-expressing strains. Soluble protein expression was achieved by optimizing the culture temperature. Subsequently, high-purity PD-1 HBc VLPs were obtained via a series of purification steps, including ammonium sulfate precipitation, size-exclusion chromatography, and anion-exchange chromatography. The expression level, protein purity, particle formation efficiency, morphological characteristics, and antigen-binding activity of the obtained PD-1 HBc VLPs were systematically characterized by electrophoresis, WB, highperformance liquid chromatography (HPLC), and transmission electron microscopy. Immunogenicity was evaluated by ELISA to determine serum antibody titers in immunized mice. CT26 colorectal carcinoma cell transplant tumor model was constructed in mice, and the anti-tumor activity of PD-1 HBc VLPs was further assessed in vivo by comparing tumor growth, body weight and tumor volume changes. Results: At 28 ℃, the soluble target protein accounted for 10.27% of total protein. The target protein was purified using Sepharose 4 Fast Flow molecular sieve and DEAE anion resin chromatography, with a purity of (91.77 ± 0.62)% and a molecular weight of 23 000. The particle size measured by electron microscopy was (31.90 ± 1.88) nm, while particle size analyzer showed a particle size of (30.66 ± 0.62) nm, and the polydispersity index (PDI) was (0.18 ± 0.05). WB analysis demonstrated that the recombinant PD-1 HBc VLPs could bind to anti-HBc VLPs serum and anti-PD-1 antibodies, respectively. ELISA results showed that on day 14 after the third immunization with PD-1 HBc VLPs, the total antibody titer in mouse serum reached 1∶640 000, with an anti-PD-1 antibody titer of 1∶40 000. Anti-tumor experiments showed that PD-1 HBc VLPs achieved a tumor inhibition rate of (27.99 ± 2.98)% in mice with colorectal carcinoma. All mice in the control group died by day 45, whereas the median survival time (MST) in the PD-1 HBc VLPs group was prolonged by 20 days. Conclusion: PD-1 HBc VLPs containing PD-1 B cell epitopes were successfully prepared and demonstrated therapeutic efficacy against colorectal cancer in mice.
2026, 33(2):147-154.
DOI: 10.3872/j.issn.1007-385X.2026.02.005
Abstract:
[Abstract] Objective: To investigate the effects of small nucleolar RNA SNORA71A on the proliferation, migration, and invasion of esophageal squamous cell carcinoma (ESCC) cells via TLR3/PD-L1 expression. Methods: qPCR was used to detect SNORA71A expression in tumor tissues, adjacent non-tumor tissues from 52 ESCC patients and human ESCC cell lines. Human ESCC TE-1 cells were transfected with antisense oligonucleotides (SNORA71A-ASO-29, SNORA71A-ASO-102, NC-ASO) or small interfering RNAs (siTLR3, siTLR3-NC), designated as SNORA71A-ASO1 group, SNORA71A-ASO2 group, NC-ASO group, and siTLR3 group, respectively. Additionally, the overexpression plasmid pcDNA3.1SNORA71A and the empty vector pcDNA3.1 were transfected into TE-1 cells, referred to as the SNORA71A group and Vector group, respectively. Cell proliferation, migration, and invasion capabilities after SNORA71A knockdown or overexpression were evaluated using cell functional assays，namely MTS, scratch wound-healing, and Transwell invasion assays. High-throughput transcriptome sequencing was performed to identify downstream target genes of SNORA71A, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were employed to predict associated biological processes and signaling pathways. qPCR was used to detect the expression of the downstream target gene TLR3 in ESCC tissues and cells. Additionally, the mRNA and protein expression levels of PD-L1 in TE-1 cells after TLR3 knockdown or overexpression were measured using qPCR and WB.Cell functional assays were performed to examine the impact of TLR3 knockdown on the malignant biological behaviors (proliferation, migration, and invasion) of TE-1 cells promoted by SNORA71A. Results: SNORA71A expression was significantly upregulated in tumor tissues from 52 ESCC patients and in ESCC cell lines (P < 0.01 or P < 0.05). Knockdown of SNORA71A inhibited TE-1 cell proliferation, migration, and invasion (P < 0.01 or P < 0.05), whereas SNORA71A overexpression promoted these malignant behaviors (P < 0.01 or P < 0.05). High-throughput transcriptome sequencing identified TLR3 as a downstream target gene of SNORA71A. TLR3 expression was significantly downregulated in ESCC tissues and TE-1 cells (P < 0.01 or P < 0.05). In addition, TLR3 positively regulated the mRNA and protein expression of PD-L1 (P < 0.01 or P < 0.05). In the cell functional assays, TLR3 partially attenuated the regulatory effect of SNORA71A on PD-L1 expression (P < 0.01). Conclusion: SNORA71A regulates the proliferation, migration and invasion of TE-1 cells by modulating the TLR3/PD-L1 pathway.
[Abstract] Objective: To investigate the effects of small nucleolar RNA SNORA71A on the proliferation, migration, and invasion of esophageal squamous cell carcinoma (ESCC) cells via TLR3/PD-L1 expression. Methods: qPCR was used to detect SNORA71A expression in tumor tissues, adjacent non-tumor tissues from 52 ESCC patients and human ESCC cell lines. Human ESCC TE-1 cells were transfected with antisense oligonucleotides (SNORA71A-ASO-29, SNORA71A-ASO-102, NC-ASO) or small interfering RNAs (siTLR3, siTLR3-NC), designated as SNORA71A-ASO1 group, SNORA71A-ASO2 group, NC-ASO group, and siTLR3 group, respectively. Additionally, the overexpression plasmid pcDNA3.1SNORA71A and the empty vector pcDNA3.1 were transfected into TE-1 cells, referred to as the SNORA71A group and Vector group, respectively. Cell proliferation, migration, and invasion capabilities after SNORA71A knockdown or overexpression were evaluated using cell functional assays，namely MTS, scratch wound-healing, and Transwell invasion assays. High-throughput transcriptome sequencing was performed to identify downstream target genes of SNORA71A, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were employed to predict associated biological processes and signaling pathways. qPCR was used to detect the expression of the downstream target gene TLR3 in ESCC tissues and cells. Additionally, the mRNA and protein expression levels of PD-L1 in TE-1 cells after TLR3 knockdown or overexpression were measured using qPCR and WB.Cell functional assays were performed to examine the impact of TLR3 knockdown on the malignant biological behaviors (proliferation, migration, and invasion) of TE-1 cells promoted by SNORA71A. Results: SNORA71A expression was significantly upregulated in tumor tissues from 52 ESCC patients and in ESCC cell lines (P < 0.01 or P < 0.05). Knockdown of SNORA71A inhibited TE-1 cell proliferation, migration, and invasion (P < 0.01 or P < 0.05), whereas SNORA71A overexpression promoted these malignant behaviors (P < 0.01 or P < 0.05). High-throughput transcriptome sequencing identified TLR3 as a downstream target gene of SNORA71A. TLR3 expression was significantly downregulated in ESCC tissues and TE-1 cells (P < 0.01 or P < 0.05). In addition, TLR3 positively regulated the mRNA and protein expression of PD-L1 (P < 0.01 or P < 0.05). In the cell functional assays, TLR3 partially attenuated the regulatory effect of SNORA71A on PD-L1 expression (P < 0.01). Conclusion: SNORA71A regulates the proliferation, migration and invasion of TE-1 cells by modulating the TLR3/PD-L1 pathway.
2026, 33(2):155-162.
DOI: 10.3872/j.issn.1007-385X.2026.02.006
Abstract:
[Abstract] Objective: To explore the efficacy and safety of anlotinib combined with immune checkpoint inhibitors (ICI) as first-line treatment for advanced lung squamous cell carcinoma (LUSC). Methods: In this single-center retrospective cohort study, 37 consecutive treatment-na?ve advanced LUSC patients treated at Fuzhou Pulmonary Hospital of Fujian between October 2018 and December 2023 were enrolled. All patients received anlotinib (8, 10, or 12 mg/d; administered for 2 weeks followed by 1 week off) combined with PD-1/PD-L1 inhibitors. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included objective response rate (ORR), disease control rate (DCR), and treatment-related adverse event (TRAE). Results: With a median follow-up of 15.2 months, the ORR reached 54.1% (20/37), the DCR was 97.3% (36/37), the median PFS was 11.8 months (95% CI: 8.3-NA), and the 12-month PFS rate was 48.6%. Exploratory subgroup analyses showed that that patients receiving anlotinib at 12 mg demonstrated significantly longer median PFS (not reached vs 7.5 months; HR = 0.09, 95% CI: 0.01-0.67; P < 0.01) and a higher ORR (100% vs 42.9%, P < 0.01) compared to those receiving 8 or 10 mg. Stage-stratified analysis showed that the ORR of patients in stage ⅢB/ⅢC disease was significantly better than those in stage Ⅳ (84.6% vs 41.7%, P = 0.02). In terms of safety, 62.2% (23/37) of the patients developed TRAE, mainly grade 1-2 hypertension (29.7%[11/37]) and hand-foot syndrome (21.6%[8/37]). Three patients (8.1%) discontinued treatment due to grade 3 TRAE. Conclusion: Anlotinib combined with ICI as a first-line treatment regimen for advanced LUSC demonstrates promising therapeutic efficacy and manageable safety profiles. Notably, in exploratory analyses, the 12 mg dose group exhibited potential signals of superior efficacy, and patients with earlier-stage disease showed a higher ORR. These findings warrant further validation through large-scale prospective studies.
[Abstract] Objective: To explore the efficacy and safety of anlotinib combined with immune checkpoint inhibitors (ICI) as first-line treatment for advanced lung squamous cell carcinoma (LUSC). Methods: In this single-center retrospective cohort study, 37 consecutive treatment-na?ve advanced LUSC patients treated at Fuzhou Pulmonary Hospital of Fujian between October 2018 and December 2023 were enrolled. All patients received anlotinib (8, 10, or 12 mg/d; administered for 2 weeks followed by 1 week off) combined with PD-1/PD-L1 inhibitors. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included objective response rate (ORR), disease control rate (DCR), and treatment-related adverse event (TRAE). Results: With a median follow-up of 15.2 months, the ORR reached 54.1% (20/37), the DCR was 97.3% (36/37), the median PFS was 11.8 months (95% CI: 8.3-NA), and the 12-month PFS rate was 48.6%. Exploratory subgroup analyses showed that that patients receiving anlotinib at 12 mg demonstrated significantly longer median PFS (not reached vs 7.5 months; HR = 0.09, 95% CI: 0.01-0.67; P < 0.01) and a higher ORR (100% vs 42.9%, P < 0.01) compared to those receiving 8 or 10 mg. Stage-stratified analysis showed that the ORR of patients in stage ⅢB/ⅢC disease was significantly better than those in stage Ⅳ (84.6% vs 41.7%, P = 0.02). In terms of safety, 62.2% (23/37) of the patients developed TRAE, mainly grade 1-2 hypertension (29.7%[11/37]) and hand-foot syndrome (21.6%[8/37]). Three patients (8.1%) discontinued treatment due to grade 3 TRAE. Conclusion: Anlotinib combined with ICI as a first-line treatment regimen for advanced LUSC demonstrates promising therapeutic efficacy and manageable safety profiles. Notably, in exploratory analyses, the 12 mg dose group exhibited potential signals of superior efficacy, and patients with earlier-stage disease showed a higher ORR. These findings warrant further validation through large-scale prospective studies.
2026, 33(2):163-169.
DOI: 10.3872/j.issn.1007-385X.2026.02.007
Abstract:
[摘 要] 免疫检查点阻断疗法的临床应用受限于其客观响应率低与耐药频发等问题。B7家族免疫检查点分子的糖基化修饰 是介导肿瘤免疫逃逸和靶向治疗抵抗的关键机制。本综述系统阐述B7家族成员特异性糖基化位点对蛋白稳定性、膜定位过程 免疫调节功能的精密调控作用，区分了N-糖基化与O-GlcNAc修饰的功能差异，并在此基础上总结了三大靶向策略：靶向糖基化 表位的中和抗体、糖基化酶抑制剂及信号通路干扰剂。临床研究显示，特异性结合PD-1的糖基化位点的卡瑞利珠单抗比不依赖 该位点的纳武利尤单抗具有更好的安全性及更优的治疗潜力，这提示阻断由异常糖基化免疫分子介导的免疫抑制通路具有重要 的应用价值。靶向B7家族免疫检查点的糖基化修饰是克服当前免疫治疗瓶颈的新范式，未来研究需着力解决靶向特异性和脱 靶毒性等挑战以推动临床转化。
[摘 要] 免疫检查点阻断疗法的临床应用受限于其客观响应率低与耐药频发等问题。B7家族免疫检查点分子的糖基化修饰 是介导肿瘤免疫逃逸和靶向治疗抵抗的关键机制。本综述系统阐述B7家族成员特异性糖基化位点对蛋白稳定性、膜定位过程 免疫调节功能的精密调控作用，区分了N-糖基化与O-GlcNAc修饰的功能差异，并在此基础上总结了三大靶向策略：靶向糖基化 表位的中和抗体、糖基化酶抑制剂及信号通路干扰剂。临床研究显示，特异性结合PD-1的糖基化位点的卡瑞利珠单抗比不依赖 该位点的纳武利尤单抗具有更好的安全性及更优的治疗潜力，这提示阻断由异常糖基化免疫分子介导的免疫抑制通路具有重要 的应用价值。靶向B7家族免疫检查点的糖基化修饰是克服当前免疫治疗瓶颈的新范式，未来研究需着力解决靶向特异性和脱 靶毒性等挑战以推动临床转化。
2026, 33(2):170-173.
DOI: 10.3872/j.issn.1007-385X.2026.02.008
Abstract:
2026, 33(2):174-180.
DOI: 10.3872/j.issn.1007-385X.2026.02.009
Abstract:
[Abstract] Objective: To investigate the expression of Shc SH2 domain-binding protein 1 (SHCBP1) in colorectal cancer (CRC) and its regulatory mechanism on Caco-2 cell proliferation, migration, and invasion. Methods: Caco-2 cells were divided into four experimental groups: the Con group (blank control), the sh-NC group (transfection with negative control sh-NC), the sh-SHCBP1 group (transfection with sh-SHCBP1), and the sh-SHCBP1 + 740Y-P group (transfection with sh-SHCBP1 followed by treatment with the PI3K activator 740Y-P at 30 μmol/L for 1 h). Cell proliferation, migration, and invasion were assessed using the CCK-8 assay, woundhealing, and Transwell invasion assay, respectively. Vasculogenic mimicry (VM) formation in Caco-2 cells was examined using a Matrigel-based three-dimensional culture system. The mRNA expression level of SHCBP1 was detected using qRT-PCR, and the protein expression levels of SHCBP1, VM-related markers, and PI3K/AKT/mTOR signaling pathway-related proteins were detected using WB. Results: SHCBP1 was significantly upregulated in CRC tissues and cell lines (P < 0.05). Compared with Con group and sh-NC group, the sh-SHCBP1 group showed significantly reduced mRNA and protein levels of SHCBP1, cell proliferation activity, wound-healing rate, number of invaded cells, and number of formed tubules (all P < 0.05). In addition, the protein expression levels of hypoxia-inducible factor 1α (HIF-1α), ephrin type-A receptor 2 (EPHA2), VEGFA, p-PI3K, p-AKT, and phosphorylated mTOR (pmTOR) were significantly decreased (all P < 0.05). Compared with the sh-SHCBP1 group, the sh-SHCBP1 + 740Y-P group demonstrated significantly increased cell proliferation, wound-healing rate, number of invaded cells, and number of formed VM structures (all P < 0.05), along with significantly elevated protein expression of HIF-1α, EPHA2, VEGFA, p-PI3K, p-AKT, and pmTOR (all P < 0.05). Conclusion: SHCBP1 is highly expressed in CRC cells and promotes the proliferation, migration, and invasion of Caco-2 cells. The underlying mechanism may be associated with activation of the PI3K/AKT/mTOR signaling pathway and subsequent promotion of the VM process.
[Abstract] Objective: To investigate the expression of Shc SH2 domain-binding protein 1 (SHCBP1) in colorectal cancer (CRC) and its regulatory mechanism on Caco-2 cell proliferation, migration, and invasion. Methods: Caco-2 cells were divided into four experimental groups: the Con group (blank control), the sh-NC group (transfection with negative control sh-NC), the sh-SHCBP1 group (transfection with sh-SHCBP1), and the sh-SHCBP1 + 740Y-P group (transfection with sh-SHCBP1 followed by treatment with the PI3K activator 740Y-P at 30 μmol/L for 1 h). Cell proliferation, migration, and invasion were assessed using the CCK-8 assay, woundhealing, and Transwell invasion assay, respectively. Vasculogenic mimicry (VM) formation in Caco-2 cells was examined using a Matrigel-based three-dimensional culture system. The mRNA expression level of SHCBP1 was detected using qRT-PCR, and the protein expression levels of SHCBP1, VM-related markers, and PI3K/AKT/mTOR signaling pathway-related proteins were detected using WB. Results: SHCBP1 was significantly upregulated in CRC tissues and cell lines (P < 0.05). Compared with Con group and sh-NC group, the sh-SHCBP1 group showed significantly reduced mRNA and protein levels of SHCBP1, cell proliferation activity, wound-healing rate, number of invaded cells, and number of formed tubules (all P < 0.05). In addition, the protein expression levels of hypoxia-inducible factor 1α (HIF-1α), ephrin type-A receptor 2 (EPHA2), VEGFA, p-PI3K, p-AKT, and phosphorylated mTOR (pmTOR) were significantly decreased (all P < 0.05). Compared with the sh-SHCBP1 group, the sh-SHCBP1 + 740Y-P group demonstrated significantly increased cell proliferation, wound-healing rate, number of invaded cells, and number of formed VM structures (all P < 0.05), along with significantly elevated protein expression of HIF-1α, EPHA2, VEGFA, p-PI3K, p-AKT, and pmTOR (all P < 0.05). Conclusion: SHCBP1 is highly expressed in CRC cells and promotes the proliferation, migration, and invasion of Caco-2 cells. The underlying mechanism may be associated with activation of the PI3K/AKT/mTOR signaling pathway and subsequent promotion of the VM process.
2026, 33(2):181-189.
DOI: 10.3872/j.issn.1007-385X.2026.02.010
Abstract:
[Abstract] Objective: To clarify the effects of mitochondrial DNA (mtDNA) partial depletion on colonic epithelial cell NCM460. Methods: Mitochondrial DNA partially depleted cell model (mtDNA-reduced) and reversion model (reverted) were established by ethidium bromide (EB) induction. Mitochondrial function was evaluated by CCK-8 (Cell Counting Kit-8) assay, reactive oxygen species (ROS) and mitochondrial membrane potential (JC-1) detection. Metabolic phenotypes were assessed by glucose, lactate and glycolytic key enzyme activity assays. Cell invasion and epithelial-mesenchymal transition (EMT) were detected by Transwell invasion assay and Western blot. Anoikis resistance was examined by polyHEMA coated culture. The PI3K/Akt/mTOR signaling pathway and programmed death ligand 1 (PD-L1) expression were detected, and verified by PI3K inhibitor LY294002. Results: GEPIA (Gene Expression Profiling Interactive Analysis) database analysis showed that mtDNA-encoded genes were down-regulated in colorectal cancer (P < 0.05). Tissue microarray showed that cytochrome coxidase subunit 1 (COX1) protein was highly expressed in normal colonic tissues but lowly expressed in cancer tissues (P < 0.05). Mitochondrial DNA-reduced NCM460 cells showed impaired mitochondrial function (decreased growth rate, reduced ROS generation, and decreased mitochondrial membrane potential, P < 0.05), exhibited the Warburg effect (increased glucose uptake, enhanced lactate secretion, and increased glycolytic key enzyme activity, P < 0.05), enhanced invasion capacity (P < 0.05) with EMT, and resisted anoikis (P < 0.05). The PI3K/Akt/mTOR pathway was activated and PD-L1 expression was upregulated in these cells. After treatment with LY294002, the glucose content showed a decreasing trend (P > 0.05), the cell activity decreased (P < 0.05), and PD-L1 expression was downregulated (P < 0.05). Conclusion: Partial depletion of mtDNA in colonic epithelial cell NCM460 can induce malignant transformation and immune escape.
[Abstract] Objective: To clarify the effects of mitochondrial DNA (mtDNA) partial depletion on colonic epithelial cell NCM460. Methods: Mitochondrial DNA partially depleted cell model (mtDNA-reduced) and reversion model (reverted) were established by ethidium bromide (EB) induction. Mitochondrial function was evaluated by CCK-8 (Cell Counting Kit-8) assay, reactive oxygen species (ROS) and mitochondrial membrane potential (JC-1) detection. Metabolic phenotypes were assessed by glucose, lactate and glycolytic key enzyme activity assays. Cell invasion and epithelial-mesenchymal transition (EMT) were detected by Transwell invasion assay and Western blot. Anoikis resistance was examined by polyHEMA coated culture. The PI3K/Akt/mTOR signaling pathway and programmed death ligand 1 (PD-L1) expression were detected, and verified by PI3K inhibitor LY294002. Results: GEPIA (Gene Expression Profiling Interactive Analysis) database analysis showed that mtDNA-encoded genes were down-regulated in colorectal cancer (P < 0.05). Tissue microarray showed that cytochrome coxidase subunit 1 (COX1) protein was highly expressed in normal colonic tissues but lowly expressed in cancer tissues (P < 0.05). Mitochondrial DNA-reduced NCM460 cells showed impaired mitochondrial function (decreased growth rate, reduced ROS generation, and decreased mitochondrial membrane potential, P < 0.05), exhibited the Warburg effect (increased glucose uptake, enhanced lactate secretion, and increased glycolytic key enzyme activity, P < 0.05), enhanced invasion capacity (P < 0.05) with EMT, and resisted anoikis (P < 0.05). The PI3K/Akt/mTOR pathway was activated and PD-L1 expression was upregulated in these cells. After treatment with LY294002, the glucose content showed a decreasing trend (P > 0.05), the cell activity decreased (P < 0.05), and PD-L1 expression was downregulated (P < 0.05). Conclusion: Partial depletion of mtDNA in colonic epithelial cell NCM460 can induce malignant transformation and immune escape.
2026, 33(2):190-198.
DOI: 10.3872/j.issn.1007-385X.2026.02.011
Abstract:
[Abstract] Objective: To investigate the effect of the green tea polyphenol epigallocatechin gallate (EGCG) on the structural changes of gut microbiota during hepatocarcinogenesis in rats. Method: A Sprague-Dawley (SD) rat model of hepatocellular carcinoma (HCC) induced by diethylnitrosamine (DEN) was established. Twenty-six SD rats were randomly divided into three groups: normal control group, HCC model group and EGCG intervention group. Starting from day 1, the EGCG group received daily intragastric administration of EGCG (40 mg/kg), while the normal control and HCC model groups received an equal volume of saline, once daily for 20 weeks. At the end of the experiment, fecal samples were collected for DNA extraction and high-throughput sequencing of the 16S rRNA gene V3-V4 region. Rats were then euthanized, livers were collected to observe tumor formation, and the incidence of HCC was calculated equencing data were processed to generate an operational taxonomic unit (OTU) table. Alpha diversity (Observed species, Chao1, Shannon, Simpson) and beta diversity were analyzed, followed by taxonomic annotation to identify compositional differences in gut microbiota among groups. Results: The liver tumor formation rate was significantly lower in the EGCG intervention group (n = 8) compared to the HCC model group (n = 10) (50% vs 100%, P = 0.023), with no tumors observed in the normal control group (n = 8). In terms of gut microbiota, the number of operational taxonomic units (OTU) in the HCC model group was significantly lower than that in the normal control group (P < 0.001), while the OTU number in the EGCG intervention group was significantly higher than that in the HCC model group (P = 0.021). Alpha diversity analysis revealed that the Shannon index was lower in the HCC model group compared to the normal control group (P < 0.05). Furthermore, compared to the HCC model group, the EGCG intervention group showed significant increases in the Observed species, Chao1, Shannon, and Simpson indices (P < 0.05). Beta diversity analysis, based on principal coordinate analysis (PCoA) and PERMANOVA (R2 = 0.3918, P = 0.001), indicated a significant separation of the gut microbiota structure among the three groups. The microbial community structure of the EGCG intervention group was positioned between the HCC model and normal control groups, clustering closer to the normal controls. The HCC model group exhibited an enrichment of potential pathobionts (e.g., Streptococcus) and a significant reduction in the abundance of butyrate-producing bacteria (e.g., Butyricicoccus, Ruminococcus) (P < 0.05) compared to the normal controls. In contrast, EGCG intervention resulted in a more stable gut microbiota structure during hepatocarcinogenesis, characterized by a significantly increased Firmicutes/Bacteroidota ratio (P < 0.05), and an enrichment of beneficial bacteria (e.g., Bifidobacterium, Lactobacillus) and butyrate-producing bacteria (e. g., Butyricicoccus). Conclusion: EGCG intervention reduces the incidence of DEN-induced HCC in rats and helps stabilize the gut microbiota structure. This effect may be associated with increased microbial diversity, promotion of beneficial and butyrate-producing bacteria, and restoration of microbial balance.
[Abstract] Objective: To investigate the effect of the green tea polyphenol epigallocatechin gallate (EGCG) on the structural changes of gut microbiota during hepatocarcinogenesis in rats. Method: A Sprague-Dawley (SD) rat model of hepatocellular carcinoma (HCC) induced by diethylnitrosamine (DEN) was established. Twenty-six SD rats were randomly divided into three groups: normal control group, HCC model group and EGCG intervention group. Starting from day 1, the EGCG group received daily intragastric administration of EGCG (40 mg/kg), while the normal control and HCC model groups received an equal volume of saline, once daily for 20 weeks. At the end of the experiment, fecal samples were collected for DNA extraction and high-throughput sequencing of the 16S rRNA gene V3-V4 region. Rats were then euthanized, livers were collected to observe tumor formation, and the incidence of HCC was calculated equencing data were processed to generate an operational taxonomic unit (OTU) table. Alpha diversity (Observed species, Chao1, Shannon, Simpson) and beta diversity were analyzed, followed by taxonomic annotation to identify compositional differences in gut microbiota among groups. Results: The liver tumor formation rate was significantly lower in the EGCG intervention group (n = 8) compared to the HCC model group (n = 10) (50% vs 100%, P = 0.023), with no tumors observed in the normal control group (n = 8). In terms of gut microbiota, the number of operational taxonomic units (OTU) in the HCC model group was significantly lower than that in the normal control group (P < 0.001), while the OTU number in the EGCG intervention group was significantly higher than that in the HCC model group (P = 0.021). Alpha diversity analysis revealed that the Shannon index was lower in the HCC model group compared to the normal control group (P < 0.05). Furthermore, compared to the HCC model group, the EGCG intervention group showed significant increases in the Observed species, Chao1, Shannon, and Simpson indices (P < 0.05). Beta diversity analysis, based on principal coordinate analysis (PCoA) and PERMANOVA (R2 = 0.3918, P = 0.001), indicated a significant separation of the gut microbiota structure among the three groups. The microbial community structure of the EGCG intervention group was positioned between the HCC model and normal control groups, clustering closer to the normal controls. The HCC model group exhibited an enrichment of potential pathobionts (e.g., Streptococcus) and a significant reduction in the abundance of butyrate-producing bacteria (e.g., Butyricicoccus, Ruminococcus) (P < 0.05) compared to the normal controls. In contrast, EGCG intervention resulted in a more stable gut microbiota structure during hepatocarcinogenesis, characterized by a significantly increased Firmicutes/Bacteroidota ratio (P < 0.05), and an enrichment of beneficial bacteria (e.g., Bifidobacterium, Lactobacillus) and butyrate-producing bacteria (e. g., Butyricicoccus). Conclusion: EGCG intervention reduces the incidence of DEN-induced HCC in rats and helps stabilize the gut microbiota structure. This effect may be associated with increased microbial diversity, promotion of beneficial and butyrate-producing bacteria, and restoration of microbial balance.
LIN Muyun
,
WU Xiuping
,
ZHENG Zifang
,
ZHENG Changyue
,
LI Kui
,
LIU Yiying
,
CHEN Haiying
,
SU Siying
,
LI Hang
2026, 33(2):199-208.
DOI: 10.3872/j.issn.1007-385X.2026.02.012
Abstract:
[Abstract] Objective: To assess the efficacy and safety of neoadjuvant therapy (NAT) with HLX02 (Zercepac? ) in combination with pertuzumab and chemotherapy for patients with HER-2-positive invasive breast carcinoma of no special type (IBC-NST), and to compare these outcomes with those of the originator trastuzumab (Herceptin? ) combined with pertuzumab. Methods: This multicenter retrospective cohort study included 132 patients with HER-2-positive breast cancer who received neoadjuvant dual HER2-targeted therapy (HLX02 or Herceptin? , both in combination with pertuzumab and chemotherapy) between May 2020 and September 2024 at the affiliated hospital of Putian University and Zhangzhou Zhengxing Hospital. The primary endpoint was the pathological complete response (pCR) rate, defined as Miller-Payne grade 5. Secondary endpoints included objective response rate (ORR, RECIST 1.1),incidence of adverse events (graded by CTCAE v5.0 and PRO-CTCAE), quality of life (EORTC QLQ-C30), and treatment costs. Statistical analysis was conducted using SPSS 27.0. To minimize baseline imbalances, propensity score matching (PSM, 1∶1 ratio) was performed to match the baseline characteristics between groups. Results: A total of 117 patients were eligible for analysis after screening (65 in the HLX02 group, 52 in the Herceptin? group). Following PSM, 42 patients remained in each group with balanced baseline characteristics. There were no significant differences in the pCR rates of the HLX02 and Herceptin? groups (66.67% vs 69.05%, P = 0.815). ORR (83.33% vs 85.71%, P = 0.763), adverse event incidence, and quality-of-life scores also showed no significant differences (all P > 0.05). However, the mean out-of-pocket cost was significantly lower in the HLX02 group compared with that in the Herceptin? group ([40 358.82 ± 15 042.69] CNY vs [51 170.20 ± 15 664.63] CNY, P = 0.002). Conclusion: This real-world study demonstrated that, in neoadjuvant therapy, HLX02 combined with pertuzumab showed comparable efficacy and similar safety compared with Herceptin? combined with pertuzumab in patients with HER-2 positive IBC-NST, and could significantly reduce the economic burden of patients, providing evidence-based medical evidence for the clinical application of domestic biosimilars.
[Abstract] Objective: To assess the efficacy and safety of neoadjuvant therapy (NAT) with HLX02 (Zercepac? ) in combination with pertuzumab and chemotherapy for patients with HER-2-positive invasive breast carcinoma of no special type (IBC-NST), and to compare these outcomes with those of the originator trastuzumab (Herceptin? ) combined with pertuzumab. Methods: This multicenter retrospective cohort study included 132 patients with HER-2-positive breast cancer who received neoadjuvant dual HER2-targeted therapy (HLX02 or Herceptin? , both in combination with pertuzumab and chemotherapy) between May 2020 and September 2024 at the affiliated hospital of Putian University and Zhangzhou Zhengxing Hospital. The primary endpoint was the pathological complete response (pCR) rate, defined as Miller-Payne grade 5. Secondary endpoints included objective response rate (ORR, RECIST 1.1),incidence of adverse events (graded by CTCAE v5.0 and PRO-CTCAE), quality of life (EORTC QLQ-C30), and treatment costs. Statistical analysis was conducted using SPSS 27.0. To minimize baseline imbalances, propensity score matching (PSM, 1∶1 ratio) was performed to match the baseline characteristics between groups. Results: A total of 117 patients were eligible for analysis after screening (65 in the HLX02 group, 52 in the Herceptin? group). Following PSM, 42 patients remained in each group with balanced baseline characteristics. There were no significant differences in the pCR rates of the HLX02 and Herceptin? groups (66.67% vs 69.05%, P = 0.815). ORR (83.33% vs 85.71%, P = 0.763), adverse event incidence, and quality-of-life scores also showed no significant differences (all P > 0.05). However, the mean out-of-pocket cost was significantly lower in the HLX02 group compared with that in the Herceptin? group ([40 358.82 ± 15 042.69] CNY vs [51 170.20 ± 15 664.63] CNY, P = 0.002). Conclusion: This real-world study demonstrated that, in neoadjuvant therapy, HLX02 combined with pertuzumab showed comparable efficacy and similar safety compared with Herceptin? combined with pertuzumab in patients with HER-2 positive IBC-NST, and could significantly reduce the economic burden of patients, providing evidence-based medical evidence for the clinical application of domestic biosimilars.
2026, 33(2):209-215.
DOI: 10.3872/j.issn.1007-385X.2026.02.013
Abstract:
[摘 要] 代谢重编程是肿瘤细胞的特征之一，与肿瘤增殖、侵袭、转移及免疫逃逸等过程密切相关。其中，脂质代谢重编程在 肿瘤免疫微环境的调控以及对免疫治疗应答的影响中发挥关键作用。肿瘤细胞通过重塑脂肪酸、胆固醇代谢等核心途径获取能 量，并构建有利于自身增殖与转移的微环境。同时，脂质代谢重编程可调控免疫细胞功能，进而影响机体抗肿瘤免疫反应。靶向 脂质代谢通路可重塑肿瘤免疫微环境，从而与免疫治疗产生协同作用，是克服免疫检查点抑制剂耐药性的潜在策略。本文系统 综述了肿瘤微环境中脂质代谢重编程在肿瘤细胞及免疫细胞中的作用机制，并总结了靶向脂质代谢联合免疫治疗的最新研究进 展，以期为探索肿瘤治疗新策略提供理论依据。
[摘 要] 代谢重编程是肿瘤细胞的特征之一，与肿瘤增殖、侵袭、转移及免疫逃逸等过程密切相关。其中，脂质代谢重编程在 肿瘤免疫微环境的调控以及对免疫治疗应答的影响中发挥关键作用。肿瘤细胞通过重塑脂肪酸、胆固醇代谢等核心途径获取能 量，并构建有利于自身增殖与转移的微环境。同时，脂质代谢重编程可调控免疫细胞功能，进而影响机体抗肿瘤免疫反应。靶向 脂质代谢通路可重塑肿瘤免疫微环境，从而与免疫治疗产生协同作用，是克服免疫检查点抑制剂耐药性的潜在策略。本文系统 综述了肿瘤微环境中脂质代谢重编程在肿瘤细胞及免疫细胞中的作用机制，并总结了靶向脂质代谢联合免疫治疗的最新研究进 展，以期为探索肿瘤治疗新策略提供理论依据。
2026, 33(2):216-224.
DOI: 10.3872/j.issn.1007-385X.2026.02.014
Abstract:
[摘 要] 胃肠道肿瘤的发病率居高不下，患者总体预后欠佳，晚期患者的治疗常受制于化疗耐药性、肿瘤内异质性及药物递送 效率有限等问题。工程化外泌体兼具天然的生物相容性、较低的免疫原性及可精准编排的靶向特性，为突破上述治疗瓶颈提供 了新型的药物递送载体，也为各类联合治疗策略提供了可灵活组合的模块化平台。在化疗中，经靶向肽修饰的工程化外泌体能 够增加药物在肿瘤组织内部的富集，还能递送siRNA、miRNA抑制剂等核酸分子，从而逆转肿瘤细胞的耐药性，并减少药物对非 靶标组织的影响。基因治疗方面，工程化改造的外泌体可携带各类核酸药物，定向调控致癌基因的表达，或抑制上皮-间充质转 化（EMT），削弱肿瘤细胞的迁移与侵袭能力。在免疫相关治疗中，工程化外泌体可通过调节巨噬细胞的极化方向及递送各类免 疫调节分子，重塑肿瘤微环境（TME），增强机体免疫应答效应。尽管工程化外泌体在这三种治疗中都表现出明显优势，但其在临 床应用阶段，仍会受到肿瘤细胞异质性较强、靶向调控手段相对单一及耐药相关分子网络过于复杂等多种因素的制约。后续研 究中需要不断更新优化工程化改造策略，搭建可实现多靶点协同作用的药物递送体系，并引入人工智能等跨学科技术工具来加 速外泌体的设计与筛选过程，从而获得效果更佳、毒性更低的个体化治疗方案。
[摘 要] 胃肠道肿瘤的发病率居高不下，患者总体预后欠佳，晚期患者的治疗常受制于化疗耐药性、肿瘤内异质性及药物递送 效率有限等问题。工程化外泌体兼具天然的生物相容性、较低的免疫原性及可精准编排的靶向特性，为突破上述治疗瓶颈提供 了新型的药物递送载体，也为各类联合治疗策略提供了可灵活组合的模块化平台。在化疗中，经靶向肽修饰的工程化外泌体能 够增加药物在肿瘤组织内部的富集，还能递送siRNA、miRNA抑制剂等核酸分子，从而逆转肿瘤细胞的耐药性，并减少药物对非 靶标组织的影响。基因治疗方面，工程化改造的外泌体可携带各类核酸药物，定向调控致癌基因的表达，或抑制上皮-间充质转 化（EMT），削弱肿瘤细胞的迁移与侵袭能力。在免疫相关治疗中，工程化外泌体可通过调节巨噬细胞的极化方向及递送各类免 疫调节分子，重塑肿瘤微环境（TME），增强机体免疫应答效应。尽管工程化外泌体在这三种治疗中都表现出明显优势，但其在临 床应用阶段，仍会受到肿瘤细胞异质性较强、靶向调控手段相对单一及耐药相关分子网络过于复杂等多种因素的制约。后续研 究中需要不断更新优化工程化改造策略，搭建可实现多靶点协同作用的药物递送体系，并引入人工智能等跨学科技术工具来加 速外泌体的设计与筛选过程，从而获得效果更佳、毒性更低的个体化治疗方案。
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- 《中国肿瘤生物治疗杂志》
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- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
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- 刊号：ISSN 1007-385X
- CN 31-1725/R
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Chinese Journal Of Cancer Biotheray ® 2026 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.