功能(生物学)
免疫监视
肿瘤微环境
细胞毒性T细胞
癌症
癌症研究
CD8型
肺癌
免疫学
生物
细胞生物学
医学
病理
免疫系统
体外
肿瘤细胞
遗传学
作者
Zhixing Hao,Zhongwei Xin,Yongyuan Chen,Zheyu Shao,Wei Lin,Wenxuan Wu,Mingjie Lin,Qinyuan Liu,Di Chen,Dang Wu,Pin Wu
标识
DOI:10.1016/j.canlet.2024.216839
摘要
Tissue-resident memory CD8+T cells (CD8+TRMs) are thought to play a crucial role in cancer immunosurveillance. However, the characteristics of CD8+TRMs in the tumor microenvironment (TME) of human non-small cell lung cancer (NSCLC) remain unclear. Here, we report that CD8+TRMs accumulate explicitly and exhibit a unique gene expression profile in the TME of NSCLC. Interestingly, these tumor-associated CD8+TRMs uniquely exhibit an innate-like phenotype. Importantly, we found that junction adhesion molecule-like (JAML) provides an alternative costimulatory signal to activate tumor-associated CD8+TRMs via combination with cancer cell-derived CXADR (CXADR Ig-like cell adhesion molecule). Furthermore, we demonstrated that activating JAML could promote the expression of TLR1/2 on CD8+TRMs, inhibit tumor progression and prolong the survival of tumor-bearing mice. Finally, we found that higher CD8+TRMs and JAML expression in the TME could predict favorable clinical outcomes in NSCLC patients. Our study reveals an intrinsic bias of CD8+TRMs for receiving the tumor-derived costimulatory signal in the TME, which sustains their innate-like function and antitumor role. These findings will shed more light on the biology of CD8+TRMs and aid in the development of potential targeted treatment strategies for NSCLC.
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