학술논문
The interaction of CD4+ helper T cells with dendritic cells shapes the tumor microenvironment and immune checkpoint blockade response
Document Type
Original Paper
Author
Cohen, Merav; Giladi, Amir; Barboy, Oren; Hamon, Pauline; Li, Baoguo; Zada, Mor; Gurevich-Shapiro, Anna; Beccaria, Cristian Gabriel; David, Eyal; Maier, Barbara B.; Buckup, Mark; Kamer, Iris; Deczkowska, Aleksandra; Le Berichel, Jessica; Bar, Jair; Iannacone, Matteo; Tanay, Amos; Merad, Miriam; Amit, Ido
Source
Nature Cancer. 3(3):303-317
Subject
Language
English
ISSN
2662-1347
Abstract
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.
Amit and colleagues report that the specific interaction of a CD4+ PD-1+ CXCL13+ T-cell subset with antigen-presenting cells reprograms the tumor microenvironment and response to immune checkpoint inhibitors in non-small cell lung cancer.
Amit and colleagues report that the specific interaction of a CD4