Tumor-associated macrophages promote intratumoral conversion of conventional CD4+ T cells into regulatory T cells via PD-1 signalling
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2022.2063225 |
| _version_ | 1818059600206757888 |
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| author | Kevin Kos Camilla Salvagno Max D. Wellenstein Muhammad A. Aslam Denize A. Meijer Cheei-Sing Hau Kim Vrijland Daphne Kaldenbach Elisabeth A.M. Raeven Martina Schmittnaegel Carola H. Ries Karin E. de Visser |
| author_facet | Kevin Kos Camilla Salvagno Max D. Wellenstein Muhammad A. Aslam Denize A. Meijer Cheei-Sing Hau Kim Vrijland Daphne Kaldenbach Elisabeth A.M. Raeven Martina Schmittnaegel Carola H. Ries Karin E. de Visser |
| author_sort | Kevin Kos |
| collection | DOAJ |
| description | 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 Tregs in 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. |
| first_indexed | 2024-12-10T13:19:06Z |
| format | Article |
| id | doaj.art-6e040c8634824418819d91cace555fe4 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-10T13:19:06Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-6e040c8634824418819d91cace555fe42022-12-22T01:47:24ZengTaylor & Francis GroupOncoImmunology2162-402X2022-12-0111110.1080/2162402X.2022.2063225Tumor-associated macrophages promote intratumoral conversion of conventional CD4+ T cells into regulatory T cells via PD-1 signallingKevin Kos0Camilla Salvagno1Max D. Wellenstein2Muhammad A. Aslam3Denize A. Meijer4Cheei-Sing Hau5Kim Vrijland6Daphne Kaldenbach7Elisabeth A.M. Raeven8Martina Schmittnaegel9Carola H. Ries10Karin E. de Visser11Division of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The NetherlandsDivision of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The NetherlandsDivision of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The NetherlandsDivision of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The NetherlandsDivision of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The NetherlandsDivision of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The NetherlandsDivision of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The NetherlandsDivision of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The NetherlandsDivision of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The NetherlandsRoche Innovation Center Munich, Roche Pharma Research and Early Development, Penzberg, GermanyRoche Innovation Center Munich, Roche Pharma Research and Early Development, Penzberg, GermanyDivision of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The NetherlandsWhile 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 Tregs in 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.https://www.tandfonline.com/doi/10.1080/2162402X.2022.2063225Breast cancer immunologyregulatory T cellstumor-associated macrophagesT cell plasticity |
| spellingShingle | Kevin Kos Camilla Salvagno Max D. Wellenstein Muhammad A. Aslam Denize A. Meijer Cheei-Sing Hau Kim Vrijland Daphne Kaldenbach Elisabeth A.M. Raeven Martina Schmittnaegel Carola H. Ries Karin E. de Visser Tumor-associated macrophages promote intratumoral conversion of conventional CD4+ T cells into regulatory T cells via PD-1 signalling OncoImmunology Breast cancer immunology regulatory T cells tumor-associated macrophages T cell plasticity |
| title | Tumor-associated macrophages promote intratumoral conversion of conventional CD4+ T cells into regulatory T cells via PD-1 signalling |
| title_full | Tumor-associated macrophages promote intratumoral conversion of conventional CD4+ T cells into regulatory T cells via PD-1 signalling |
| title_fullStr | Tumor-associated macrophages promote intratumoral conversion of conventional CD4+ T cells into regulatory T cells via PD-1 signalling |
| title_full_unstemmed | Tumor-associated macrophages promote intratumoral conversion of conventional CD4+ T cells into regulatory T cells via PD-1 signalling |
| title_short | Tumor-associated macrophages promote intratumoral conversion of conventional CD4+ T cells into regulatory T cells via PD-1 signalling |
| title_sort | tumor associated macrophages promote intratumoral conversion of conventional cd4 t cells into regulatory t cells via pd 1 signalling |
| topic | Breast cancer immunology regulatory T cells tumor-associated macrophages T cell plasticity |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2022.2063225 |
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