MINI REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1604310
This article is part of the Research TopicExploring immune low-response states through single-cell technologies and spatial transcriptomicsView all 3 articles
T Lymphocyte Heterogeneity in NSCLC: Implications for Biomarker Development and Therapeutic Innovation
Provisionally accepted
- 1Center for Translational Medicine, Guangxi Medical University, Nanning, Guangxi 530021, China, Nanning, China
- 2Key Laboratory of Longevity and Ageing-Related Disease, Ministry of Education, Guangxi Medical University, Nannning, Guangx, China
- 3Guangxi Key Laboratory of Brain Science, Guangxi Medical University, Nanning, Guangxi 530021, China, Nanning, China
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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.
Keywords: Melanoma, T lymphocyte, CD8 + T cell, PD-1, NRAS mutations; Immunotherapy Combination therapy, biomarkers
Received: 01 Apr 2025; Accepted: 12 May 2025.
Copyright: © 2025 Liu, Qin and Fu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jiejun Fu, Center for Translational Medicine, Guangxi Medical University, Nanning, Guangxi 530021, China, Nanning, China
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