Jiaoyun Lv, Wencheng Yin, Xialin Nie, Siyuan Chen, Yuqi Zhong, Shufa Yang, Ziyi He, Yanhong Yao, Qiqi Wang, Yang Zhao, Hui Dai
Peripheral T cell profiles reflect antitumour immunity, yet systemic immune shifts often remain confounded by demographic factors. This study aimed to delineate true tumour-driven T cell alterations in lung cancer. We analysed peripheral blood from 121 lung cancer patients and strictly age- and sex-matched healthy controls using multiparametric flow cytometry, corroborated by human lung cancer spatial transcriptomics (ST). Following demographic standardisation, patients exhibited a systemic T cell priming blockade, characterised by significantly accumulated naïve T cells and depleted effector memory T cells (CD4+ p < 0.01; CD8+ p < 0.0001). Conversely, Th17.1 cells and immune checkpoints (e.g., PD-1, CTLA-4) were robustly elevated. Crucially, ST validated a striking intratumoural spatial accumulation of Th17.1 cells. We conclude that the peripheral expansion of Th17.1 cells is a genuine tumour-driven event that faithfully mirrors local tumour microenvironment remodelling and potential Tertiary Lymphoid Structure (TLS) neogenesis. This positions peripheral Th17.1 profiling as a valuable, noninvasive biomarker for evaluating systemic immunosuppression and guiding personalised immunotherapy.