The Interaction of CD4 Helper T Cells with Dendritic Cells Shapes the Tumor Microenvironment and Immune Checkpoint Blockade Response

Overview

Journal Nat Cancer

Specialty Oncology

Date 2022 Mar 4

PMID 35241835

Authors

Merav Cohen

Amir Giladi

Oren Barboy

Pauline Hamon

Baoguo Li

Mor Zada

Anna Gurevich-Shapiro

Cristian Gabriel Beccaria

Eyal David

Barbara B Maier

Mark Buckup

Iris Kamer

Aleksandra Deczkowska

Jessica Le Berichel

Jair Bar

Matteo Iannacone

Amos Tanay

Miriam Merad

Ido Amit

Affiliations

Soon will be listed here.

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 CD4PD-1CXCL13 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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