Tumor-infiltrating lymphocytes in NSCLC: from immune surveillance to immunotherapy
Lung cancer, predominantly non-small cell lung cancer (NSCLC), remains a principal driver of cancer-related morbidity and mortality worldwide. Despite advancements in surgery, radiotherapy, chemotherapy, and targeted treatments, outcomes remain poor in advanced NSCLC. The tumor microenvironment (TME...
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| Format: | Article |
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1610998/full |
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| author | Haiyi Xue Yilan Fan Yi Li Qian Zhao Xuelu Zhang Pei Zhao Zhenjun Liu |
| author_facet | Haiyi Xue Yilan Fan Yi Li Qian Zhao Xuelu Zhang Pei Zhao Zhenjun Liu |
| author_sort | Haiyi Xue |
| collection | DOAJ |
| description | Lung cancer, predominantly non-small cell lung cancer (NSCLC), remains a principal driver of cancer-related morbidity and mortality worldwide. Despite advancements in surgery, radiotherapy, chemotherapy, and targeted treatments, outcomes remain poor in advanced NSCLC. The tumor microenvironment (TME) exerts a critical influence on therapy responses. Within the TME, immune cells such as T and B lymphocytes, dendritic cells, myeloid-derived suppressor cells, tumor-associated macrophages, neutrophils, and natural killer cells can drive both pro- and anti-tumor processes. This review integrates their classification, phenotypic plasticity, and roles in NSCLC, highlighting key preclinical and clinical evidence while discussing pathogenesis, prognostic significance, and therapeutic potential. We also summarize the current immunotherapeutic strategies for advanced NSCLC, including first- or second-line regimens with immune checkpoint inhibitors alone or combined with chemotherapy, anti-angiogenic agents, or additional checkpoint inhibitors, and future directions. By elucidating the interplay between the NSCLC immune microenvironment and emerging immunotherapies, this review emphasizes the need for novel combination regimens and robust predictive biomarkers to improve clinical outcomes and extend survival in advanced NSCLC. |
| format | Article |
| id | doaj-art-7ceff81b8c87470dbebadbfa01deee68 |
| 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-7ceff81b8c87470dbebadbfa01deee682025-08-20T03:32:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16109981610998Tumor-infiltrating lymphocytes in NSCLC: from immune surveillance to immunotherapyHaiyi Xue0Yilan Fan1Yi Li2Qian Zhao3Xuelu Zhang4Pei Zhao5Zhenjun Liu6Department of Intensive Care Unit, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of General Medicine, MianYang Cancer Hospital, Mianyang, ChinaDepartment of Intensive Care Unit, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Intensive Care Unit, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Intensive Care Unit, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Intensive Care Unit, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Intensive Care Unit, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, ChinaLung cancer, predominantly non-small cell lung cancer (NSCLC), remains a principal driver of cancer-related morbidity and mortality worldwide. Despite advancements in surgery, radiotherapy, chemotherapy, and targeted treatments, outcomes remain poor in advanced NSCLC. The tumor microenvironment (TME) exerts a critical influence on therapy responses. Within the TME, immune cells such as T and B lymphocytes, dendritic cells, myeloid-derived suppressor cells, tumor-associated macrophages, neutrophils, and natural killer cells can drive both pro- and anti-tumor processes. This review integrates their classification, phenotypic plasticity, and roles in NSCLC, highlighting key preclinical and clinical evidence while discussing pathogenesis, prognostic significance, and therapeutic potential. We also summarize the current immunotherapeutic strategies for advanced NSCLC, including first- or second-line regimens with immune checkpoint inhibitors alone or combined with chemotherapy, anti-angiogenic agents, or additional checkpoint inhibitors, and future directions. By elucidating the interplay between the NSCLC immune microenvironment and emerging immunotherapies, this review emphasizes the need for novel combination regimens and robust predictive biomarkers to improve clinical outcomes and extend survival in advanced NSCLC.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1610998/fulllung cancertumor microenvironmentimmune cellsimmunotherapyCD8 + T cellB cell |
| spellingShingle | Haiyi Xue Yilan Fan Yi Li Qian Zhao Xuelu Zhang Pei Zhao Zhenjun Liu Tumor-infiltrating lymphocytes in NSCLC: from immune surveillance to immunotherapy Frontiers in Immunology lung cancer tumor microenvironment immune cells immunotherapy CD8 + T cell B cell |
| title | Tumor-infiltrating lymphocytes in NSCLC: from immune surveillance to immunotherapy |
| title_full | Tumor-infiltrating lymphocytes in NSCLC: from immune surveillance to immunotherapy |
| title_fullStr | Tumor-infiltrating lymphocytes in NSCLC: from immune surveillance to immunotherapy |
| title_full_unstemmed | Tumor-infiltrating lymphocytes in NSCLC: from immune surveillance to immunotherapy |
| title_short | Tumor-infiltrating lymphocytes in NSCLC: from immune surveillance to immunotherapy |
| title_sort | tumor infiltrating lymphocytes in nsclc from immune surveillance to immunotherapy |
| topic | lung cancer tumor microenvironment immune cells immunotherapy CD8 + T cell B cell |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1610998/full |
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