Tumor-infiltrated double-negative regulatory T cells predict outcome of T cell-based immunotherapy in nasopharyngeal carcinoma

文献类型： 外文期刊

第一作者： Liu, Xiu-Feng

作者： Liu, Xiu-Feng;Zhu, Qian;He, Jia;Zeng, Xi-Liang;Li, Jiang;Liang, Yu-Jing;Chen, Qiu-Yan;Mai, Hai-Qiang;Song, Bin;Yue, Jian-Hui;Qin, Ye-Chi;Zhang, Xi;Sun, Chang-Bin;Song, Bin

作者机构：

期刊名称：CELL REPORTS MEDICINE （ 影响因子：10.6； 五年影响因子：10.8 ）

ISSN： 2666-3791

年卷期： 2025 年 6 卷 5 期

页码：

收录情况： SCI

摘要： Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) has demonstrated clinical success in solid tumors. We analyze 47 TIL infusion products and 62 pretreatment tumor microenvironments (TMEs) from a randomized phase 2 clinical study of concurrent chemoradiotherapy plus TIL-ACT (NCT02421640). Using single-cell and bulk RNA sequencing along with flow cytometry, we identify 14 CD3+ T cell clusters within 26 TIL infusion products: 11 CD3+CD8+ TILs, 2 CD3+CD4+ TILs, and 1 CD3+CD8-CD4-double-negative (DN) TIL. (DN) TILs, significantly associated with poor TIL-ACT outcomes, exhibit an activated regulatory T cell-like phenotype and include two CD56+ and four CD56-subsets. Among them, CD56-KZF2+ (DN) TILs are predominantly suppressive. (DN) TILs inhibit CD8+ TIL expansion via Fas-FasL, transforming growth factor beta (TGF-beta), and interleukin (IL)-10 signaling. Distinct CD8+ T subsets differentially impact on TIL-ACT outcomes, while 9 baseline TME gene signatures and 14 intracellularT cell genes hold prognostic value. Our findings identify predictive TIL subsets and biomarkers for TIL-ACT outcomes.

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