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© Research
Publication : Nature cancer

The interaction of CD4+ helper T cells with dendritic cells shapes the tumor microenvironment and immune checkpoint blockade response.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nature cancer - 01 Mar 2022

Cohen M, Giladi A, Barboy O, Hamon P, Li B, Zada M, Gurevich-Shapiro A, Beccaria CG, David E, Maier BB, Buckup M, Kamer I, Deczkowska A, Le Berichel J, Bar J, Iannacone M, Tanay A, Merad M, Amit I,

Link to Pubmed [PMID] – 35241835

Link to DOI – 10.1038/s43018-022-00338-5

Nat Cancer 2022 03; 3(3): 303-317

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.

https://pubmed.ncbi.nlm.nih.gov/35241835