T lymphocyte heterogeneity in NSCLC: implications for biomarker development and therapeutic innovation
Non-small cell lung cancer (NSCLC) immunotherapy has been revolutionized by immune checkpoint inhibitors (ICIs), yet response heterogeneity persists due to dynamic tumor-immune interactions. This review summarizes recent studies in understanding tumor-infiltrating lymphocyte (TIL) biology, highlight...
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| Format: | Article |
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1604310/full |
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| author | Yu Liu Yu Liu Denghui Qin Denghui Qin Jiejun Fu Jiejun Fu Jiejun Fu |
| author_facet | Yu Liu Yu Liu Denghui Qin Denghui Qin Jiejun Fu Jiejun Fu Jiejun Fu |
| author_sort | Yu Liu |
| collection | DOAJ |
| description | Non-small cell lung cancer (NSCLC) immunotherapy has been revolutionized by immune checkpoint inhibitors (ICIs), yet response heterogeneity persists due to dynamic tumor-immune interactions. This review summarizes recent studies in understanding tumor-infiltrating lymphocyte (TIL) biology, highlighting CD8+ cytotoxic T cells and regulatory T cells (Tregs) as pivotal regulators of immune surveillance and suppression. We summarize emerging biomarkers such as TCR clonality, spatial distribution of tumor-infiltrating lymphocytes (TILs), and exhaustion markers including PD-1, TCF1, and TIM-3, which predict immune checkpoint inhibitor (ICI) efficacy beyond PD-L1 expression. This review specifically describes radiotherapy-induced immunogenic remodeling and peripheral T cell dynamics as innovative strategies to monitor immune response and resistance mechanisms. By integrating results from single-cell omics and AI-driven spatial analysis, we propose multidimensional frameworks of TIL in NSCLC to overcome resistance and optimize immunotherapy combinations. These insights collectively advance NSCLC immunotherapy toward precision modulation of the tumor immune microenvironment. |
| format | Article |
| id | doaj-art-1cae6486f6e44a7d8207d2f3fc7f6343 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-1cae6486f6e44a7d8207d2f3fc7f63432025-08-20T02:38:21ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.16043101604310T lymphocyte heterogeneity in NSCLC: implications for biomarker development and therapeutic innovationYu Liu0Yu Liu1Denghui Qin2Denghui Qin3Jiejun Fu4Jiejun Fu5Jiejun Fu6Center for Translational Medicine, Guangxi Medical University, Nanning, Guangxi, ChinaKey Laboratory of Longevity and Aging-Related Diseases, Ministry of Education, Nanning, Guangxi, ChinaCenter for Translational Medicine, Guangxi Medical University, Nanning, Guangxi, ChinaKey Laboratory of Longevity and Aging-Related Diseases, Ministry of Education, Nanning, Guangxi, ChinaCenter for Translational Medicine, Guangxi Medical University, Nanning, Guangxi, ChinaKey Laboratory of Longevity and Aging-Related Diseases, Ministry of Education, Nanning, Guangxi, ChinaGuangxi Key Laboratory of Brain Science, Guangxi Medical University, Nanning, Guangxi, ChinaNon-small cell lung cancer (NSCLC) immunotherapy has been revolutionized by immune checkpoint inhibitors (ICIs), yet response heterogeneity persists due to dynamic tumor-immune interactions. This review summarizes recent studies in understanding tumor-infiltrating lymphocyte (TIL) biology, highlighting CD8+ cytotoxic T cells and regulatory T cells (Tregs) as pivotal regulators of immune surveillance and suppression. We summarize emerging biomarkers such as TCR clonality, spatial distribution of tumor-infiltrating lymphocytes (TILs), and exhaustion markers including PD-1, TCF1, and TIM-3, which predict immune checkpoint inhibitor (ICI) efficacy beyond PD-L1 expression. This review specifically describes radiotherapy-induced immunogenic remodeling and peripheral T cell dynamics as innovative strategies to monitor immune response and resistance mechanisms. By integrating results from single-cell omics and AI-driven spatial analysis, we propose multidimensional frameworks of TIL in NSCLC to overcome resistance and optimize immunotherapy combinations. These insights collectively advance NSCLC immunotherapy toward precision modulation of the tumor immune microenvironment.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1604310/fullmelanomaT lymphocyteCD8 + T cellPD-1NRAS mutationsimmunotherapy combination therapy |
| spellingShingle | Yu Liu Yu Liu Denghui Qin Denghui Qin Jiejun Fu Jiejun Fu Jiejun Fu T lymphocyte heterogeneity in NSCLC: implications for biomarker development and therapeutic innovation Frontiers in Immunology melanoma T lymphocyte CD8 + T cell PD-1 NRAS mutations immunotherapy combination therapy |
| title | T lymphocyte heterogeneity in NSCLC: implications for biomarker development and therapeutic innovation |
| title_full | T lymphocyte heterogeneity in NSCLC: implications for biomarker development and therapeutic innovation |
| title_fullStr | T lymphocyte heterogeneity in NSCLC: implications for biomarker development and therapeutic innovation |
| title_full_unstemmed | T lymphocyte heterogeneity in NSCLC: implications for biomarker development and therapeutic innovation |
| title_short | T lymphocyte heterogeneity in NSCLC: implications for biomarker development and therapeutic innovation |
| title_sort | t lymphocyte heterogeneity in nsclc implications for biomarker development and therapeutic innovation |
| topic | melanoma T lymphocyte CD8 + T cell PD-1 NRAS mutations immunotherapy combination therapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1604310/full |
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