Research progress on mechanisms of tumor immune microenvironment and gastrointestinal resistance to immunotherapy: mini review
Gastrointestinal (GI) tumors present a major clinical challenge due to complex immune evasion mechanisms and generally poor responses to immunotherapy. Tumor immune microenvironment (TIME) is a critical determinant of immunotherapy resistance. Immunosuppressive cell populations such as regulatory T...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-07-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1641518/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849304184259608576 |
|---|---|
| author | Zheng Zhang Yangping Wu |
| author_facet | Zheng Zhang Yangping Wu |
| author_sort | Zheng Zhang |
| collection | DOAJ |
| description | Gastrointestinal (GI) tumors present a major clinical challenge due to complex immune evasion mechanisms and generally poor responses to immunotherapy. Tumor immune microenvironment (TIME) is a critical determinant of immunotherapy resistance. Immunosuppressive cell populations such as regulatory T cells, M2-polarized tumor-associated macrophages, and cancer-associated fibroblasts, together with aberrant cytokine networks and mechanical stress in the tumor stroma, cooperate to exclude T-cell infiltration and induce T-cell exhaustion, thereby undermining the efficacy of immune checkpoint inhibitors. In addition, TIME-driven signaling pathway activation and epigenetic reprogramming further reinforce immune escape and therapeutic failure. Recent advances in single-cell and spatial transcriptomic technologies have greatly improved our understanding of these processes. Meanwhile, strategies including multi-target combination immunotherapies, epigenetic modulators, mRNA vaccines, and gut microbiota interventions are under active investigation to reverse resistance and remodel the TIME. This mini review summarizes the multifaceted mechanisms of immunotherapy resistance in GI tumors and discusses the potential of emerging therapeutic strategies to improve clinical outcomes. |
| format | Article |
| id | doaj-art-5f5da63fcc114b2abcd0827fccedb9d1 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-5f5da63fcc114b2abcd0827fccedb9d12025-08-20T03:55:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16415181641518Research progress on mechanisms of tumor immune microenvironment and gastrointestinal resistance to immunotherapy: mini reviewZheng Zhang0Yangping Wu1Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Pulmonary and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Precision Medicine Key Laboratory of Sichuan Province and Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaGastrointestinal (GI) tumors present a major clinical challenge due to complex immune evasion mechanisms and generally poor responses to immunotherapy. Tumor immune microenvironment (TIME) is a critical determinant of immunotherapy resistance. Immunosuppressive cell populations such as regulatory T cells, M2-polarized tumor-associated macrophages, and cancer-associated fibroblasts, together with aberrant cytokine networks and mechanical stress in the tumor stroma, cooperate to exclude T-cell infiltration and induce T-cell exhaustion, thereby undermining the efficacy of immune checkpoint inhibitors. In addition, TIME-driven signaling pathway activation and epigenetic reprogramming further reinforce immune escape and therapeutic failure. Recent advances in single-cell and spatial transcriptomic technologies have greatly improved our understanding of these processes. Meanwhile, strategies including multi-target combination immunotherapies, epigenetic modulators, mRNA vaccines, and gut microbiota interventions are under active investigation to reverse resistance and remodel the TIME. This mini review summarizes the multifaceted mechanisms of immunotherapy resistance in GI tumors and discusses the potential of emerging therapeutic strategies to improve clinical outcomes.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1641518/fullgastrointestinal tumorstumor immune microenvironmentimmunotherapy resistanceimmune checkpoint inhibitorscombination therapymRNA vaccines |
| spellingShingle | Zheng Zhang Yangping Wu Research progress on mechanisms of tumor immune microenvironment and gastrointestinal resistance to immunotherapy: mini review Frontiers in Immunology gastrointestinal tumors tumor immune microenvironment immunotherapy resistance immune checkpoint inhibitors combination therapy mRNA vaccines |
| title | Research progress on mechanisms of tumor immune microenvironment and gastrointestinal resistance to immunotherapy: mini review |
| title_full | Research progress on mechanisms of tumor immune microenvironment and gastrointestinal resistance to immunotherapy: mini review |
| title_fullStr | Research progress on mechanisms of tumor immune microenvironment and gastrointestinal resistance to immunotherapy: mini review |
| title_full_unstemmed | Research progress on mechanisms of tumor immune microenvironment and gastrointestinal resistance to immunotherapy: mini review |
| title_short | Research progress on mechanisms of tumor immune microenvironment and gastrointestinal resistance to immunotherapy: mini review |
| title_sort | research progress on mechanisms of tumor immune microenvironment and gastrointestinal resistance to immunotherapy mini review |
| topic | gastrointestinal tumors tumor immune microenvironment immunotherapy resistance immune checkpoint inhibitors combination therapy mRNA vaccines |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1641518/full |
| work_keys_str_mv | AT zhengzhang researchprogressonmechanismsoftumorimmunemicroenvironmentandgastrointestinalresistancetoimmunotherapyminireview AT yangpingwu researchprogressonmechanismsoftumorimmunemicroenvironmentandgastrointestinalresistancetoimmunotherapyminireview |