Tumor-associated macrophages promote intratumoral conversion of conventional CD4+ T cells into regulatory T cells via PD-1 signalling

While regulatory T cells (T regs ) 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 macrophage...

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Published in:Oncoimmunology Vol. 11; no. 1; p. 2063225
Main 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.
Format: Journal Article
Language:English
Published: United States Taylor & Francis 31.12.2022
Taylor & Francis Group
Subjects:
Breast cancer immunology
Breast Neoplasms
Female
Humans
Immune Tolerance
Original Research
Programmed Cell Death 1 Receptor
regulatory T cells
T cell plasticity
T-Lymphocytes, Regulatory
Tumor Microenvironment
Tumor-Associated Macrophages
regulatory T cells
Breast cancer immunology
T cell plasticity
tumor-associated macrophages
ISSN:2162-402X, 2162-4011, 2162-402X
Online Access:Get full text
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Summary:While regulatory T cells (T regs ) 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 T regs by promoting the conversion of conventional CD4 + T cells (T convs ) into T regs . Mechanistically, two processes were identified that independently contribute to this process. While TAM-derived TGF-β directly promotes the conversion of CD4 + T convs into T regs in vitro, we additionally show that TAMs enhance PD-1 expression on CD4 + T cells. This indirectly contributes to the intratumoral accumulation of T regs , as loss of PD-1 on CD4 + T convs abrogates intratumoral conversion of adoptively transferred CD4 + T convs into T regs . 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 T regs in breast tumors.
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ISSN:2162-402X
2162-4011
2162-402X
DOI:10.1080/2162402X.2022.2063225