Tumor-associated macrophages promote intratumoral conversion of conventional CD4+ T cells into regulatory T cells via PD-1 signalling. Academic Article uri icon

Overview

abstract

  • While regulatory T cells (Tregs) and macrophages have been recognized as key orchestrators of cancer-associated immunosuppression, their cellular crosstalk within tumors has been poorly characterized. Here, using spontaneous models for breast cancer, we demonstrate that tumor-associated macrophages (TAMs) contribute to the intratumoral accumulation of Tregs by promoting the conversion of conventional CD4+ T cells (Tconvs) into Tregs. Mechanistically, two processes were identified that independently contribute to this process. While TAM-derived TGF-β directly promotes the conversion of CD4+ Tconvs into Tregsin vitro, we additionally show that TAMs enhance PD-1 expression on CD4+ T cells. This indirectly contributes to the intratumoral accumulation of Tregs, as loss of PD-1 on CD4+ Tconvs abrogates intratumoral conversion of adoptively transferred CD4+ Tconvs into Tregs. Combined, this study provides insights into the complex immune cell crosstalk between CD4+ T cells and TAMs in the tumor microenvironment of breast cancer, and further highlights that therapeutic exploitation of macrophages may be an attractive immune intervention to limit the accumulation of Tregs in breast tumors.

authors

  • Kos, Kevin
  • Salvagno, Camilla
  • Wellenstein, Max D
  • Aslam, Muhammad A
  • Meijer, Denize A
  • Hau, Cheei-Sing
  • Vrijland, Kim
  • Kaldenbach, Daphne
  • Raeven, Elisabeth A M
  • Schmittnaegel, Martina
  • Ries, Carola H
  • de Visser, Karin E

publication date

  • April 15, 2022

Research

keywords

  • Breast Neoplasms
  • T-Lymphocytes, Regulatory

Identity

PubMed Central ID

  • PMC9037432

Scopus Document Identifier

  • 85128433439

Digital Object Identifier (DOI)

  • 10.1073/pnas.2004810117

PubMed ID

  • 35481289

Additional Document Info

volume

  • 11

issue

  • 1