CXCR3 Expression in Regulatory T cells Drives Interactions with Type I Dendritic Cells in Tumors to Restrict CD8 T cell Antitumor Immunity

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2023 Jul 1

PMID 37392735

Authors

Mariela A Moreno Ayala

Timothy F Campbell

Chenyu Zhang

Noa Dahan

Alissa Bockman

Varsha Prakash

Lawrence Feng

Theo Sher

Michel DuPage

Affiliations

Soon will be listed here.

Abstract

Infiltration of regulatory T (Treg) cells, an immunosuppressive population of CD4 T cells, into solid cancers represents a barrier to cancer immunotherapy. Chemokine receptors are critical for Treg cell recruitment and cell-cell interactions in inflamed tissues, including cancer, and thus are an ideal therapeutic target. Here, we show in multiple cancer models that CXCR3 Treg cells were increased in tumors compared with lymphoid tissues, exhibited an activated phenotype, and interacted preferentially with CXCL9-producing BATF3 dendritic cells (DCs). Genetic ablation of CXCR3 in Treg cells disrupted DC1-Treg cell interactions and concomitantly increased DC-CD8 T cell interactions. Mechanistically, CXCR3 ablation in Treg cells increased tumor antigen-specific cross-presentation by DC1s, increasing CD8 T cell priming and reactivation in tumors. This ultimately impaired tumor progression, especially in combination with anti-PD-1 checkpoint blockade immunotherapy. Overall, CXCR3 is shown to be a critical chemokine receptor for Treg cell accumulation and immune suppression in tumors.

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