免疫系统
癌症研究
肿瘤微环境
滤泡树突状细胞
抗原呈递
生物
肿瘤抗原
T细胞
免疫疗法
抗原
免疫学
抗原提呈细胞
化学
细胞生物学
作者
Michal Cohen,Amir Giladi,Oren Barboy,Pauline Hamon,Baoguo Li,Mor Zada,Anna Gurevich-Shapiro,Cristian Gabriel Beccaria,Eyal David,Bárbara Maier,Mark Buckup,Iris Kamer,Aleksandra Deczkowska,Jessica Le Bérichel,Jair Bar,Matteo Iannacone,Amos Tanay,Miriam Mérad,Ido Amit
出处
期刊:Nature cancer
[Springer Nature]
日期:2022-03-03
卷期号:3 (3): 303-317
被引量:86
标识
DOI:10.1038/s43018-022-00338-5
摘要
Despite their key regulatory role and therapeutic potency, the molecular signatures of interactions between T cells and antigen-presenting myeloid cells within the tumor microenvironment remain poorly characterized. Here, we systematically characterize these interactions using RNA sequencing of physically interacting cells (PIC-seq) and find that CD4+PD-1+CXCL13+ T cells are a major interacting hub with antigen-presenting cells in the tumor microenvironment of human non-small cell lung carcinoma. We define this clonally expanded, tumor-specific and conserved T-cell subset as T-helper tumor (Tht) cells. Reconstitution of Tht cells in vitro and in an ovalbumin-specific αβ TCR CD4+ T-cell mouse model, shows that the Tht program is primed in tumor-draining lymph nodes by dendritic cells presenting tumor antigens, and that their function is important for harnessing the antitumor response of anti-PD-1 treatment. Our molecular and functional findings support the modulation of Tht-dendritic cell interaction checkpoints as a major interventional strategy in immunotherapy.
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