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
作者： Liu, Xiu-Feng 1 ; Song, Bin 3 ; Sun, Chang-Bin 4 ; Zhu, Qian 1 ; Yue, Jian-Hui 3 ; Liang, Yu-Jing 2 ; He, Jia 1 ; Zeng, Xi-Liang 1 ; Qin, Ye-Chi 3 ; Chen, Qiu-Yan 2 ; Mai, Hai-Qiang 2 ; Zhang, Xi 3 ; Li, Jiang 1 ;
作者机构： 1.Sun Yat Sen Univ Canc Ctr, Guangdong Prov Clin Res Ctr Canc, Collaborat Innovat Ctr Canc Med, Dept Biotherapy,State Key Lab Oncol South China,Gu, Guangzhou 510060, Peoples R China
2.Sun Yat Sen Univ Canc Ctr, Guangdong Prov Clin Res Ctr Canc, Collaborat Innovat Ctr Canc Med, Dept Nasopharyngeal Carcinoma,State Key Lab Oncol, Guangzhou 510060, Peoples R China
3.BGI, Shenzhen 518083, Peoples R China
4.Chinese Acad Agr Sci, Agr Genom Inst Shenzhen, Shenzhen Branch, Guangdong Lab Lingnan Modern Agr,Minist Agr & Rura, Shenzhen 518120, Peoples R China
5.Univ Chinese Acad Sci, Coll Life Sci, Beijing 100049, Peoples R China
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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