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Tumor-Infiltrating Myeloid Cells Co-Express TREM1 and TREM2 and Elevated TREM-1 Associates With Disease Progression in Renal Cell Carcinoma
Myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) contribute to cancer-related inflammation and tumor progression. While several myeloid molecules have been ascribed a regulatory function in these processes, the triggering receptors expressed on myeloid cells (TREMs) hav...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8867210/ https://www.ncbi.nlm.nih.gov/pubmed/35223446 http://dx.doi.org/10.3389/fonc.2021.662723 |
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author | Ford, Jill W. Gonzalez-Cotto, Marieli MacFarlane, Alexander W. Peri, Suraj Howard, O. M. Zack Subleski, Jeffrey J. Ruth, Karen J. Haseebuddin, Mohammed Al-Saleem, Tahseen Yang, Youfeng Rayman, Pat Rini, Brian Linehan, W. Marston Finke, James Weiss, Jonathan M. Campbell, Kerry S. McVicar, Daniel W. |
author_facet | Ford, Jill W. Gonzalez-Cotto, Marieli MacFarlane, Alexander W. Peri, Suraj Howard, O. M. Zack Subleski, Jeffrey J. Ruth, Karen J. Haseebuddin, Mohammed Al-Saleem, Tahseen Yang, Youfeng Rayman, Pat Rini, Brian Linehan, W. Marston Finke, James Weiss, Jonathan M. Campbell, Kerry S. McVicar, Daniel W. |
author_sort | Ford, Jill W. |
collection | PubMed |
description | Myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) contribute to cancer-related inflammation and tumor progression. While several myeloid molecules have been ascribed a regulatory function in these processes, the triggering receptors expressed on myeloid cells (TREMs) have emerged as potent modulators of the innate immune response. While various TREMs amplify inflammation, others dampen it and are emerging as important players in modulating tumor progression—for instance, soluble TREM-1 (sTREM-1), which is detected during inflammation, associates with disease progression, while TREM-2 expression is associated with tumor-promoting macrophages. We hypothesized that TREM-1 and TREM-2 might be co-expressed on tumor-infiltrating myeloid cells and that elevated sTREM-1 associates with disease outcomes, thus representing a possibility for mutual modulation in cancer. Using the 4T1 breast cancer model, we found TREM-1 and TREM-2 expression on MDSC and TAM and that sTREM-1 was elevated in tumor-bearing mice in multiple models and correlated with tumor volume. While TREM-1 engagement enhanced TNF, a TREM-2 ligand was detected on MDSC and TAM, suggesting that both TREM could be functional in the tumor setting. Similarly, we detected TREM-1 and Trem2 expression in myeloid cells in the RENCA model of renal cell carcinoma (RCC). We confirmed these findings in human disease by demonstrating the expression of TREM-1 on tumor-infiltrating myeloid cells from patients with RCC and finding that sTREM-1 was increased in patients with RCC. Finally, The Cancer Genome Atlas analysis shows that TREM1 expression in tumors correlates with poor outcomes in RCC. Taken together, our data suggest that manipulation of the TREM-1/TREM-2 balance in tumors may be a novel means to modulate tumor-infiltrating myeloid cell phenotype and function. |
format | Online Article Text |
id | pubmed-8867210 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88672102022-02-25 Tumor-Infiltrating Myeloid Cells Co-Express TREM1 and TREM2 and Elevated TREM-1 Associates With Disease Progression in Renal Cell Carcinoma Ford, Jill W. Gonzalez-Cotto, Marieli MacFarlane, Alexander W. Peri, Suraj Howard, O. M. Zack Subleski, Jeffrey J. Ruth, Karen J. Haseebuddin, Mohammed Al-Saleem, Tahseen Yang, Youfeng Rayman, Pat Rini, Brian Linehan, W. Marston Finke, James Weiss, Jonathan M. Campbell, Kerry S. McVicar, Daniel W. Front Oncol Oncology Myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) contribute to cancer-related inflammation and tumor progression. While several myeloid molecules have been ascribed a regulatory function in these processes, the triggering receptors expressed on myeloid cells (TREMs) have emerged as potent modulators of the innate immune response. While various TREMs amplify inflammation, others dampen it and are emerging as important players in modulating tumor progression—for instance, soluble TREM-1 (sTREM-1), which is detected during inflammation, associates with disease progression, while TREM-2 expression is associated with tumor-promoting macrophages. We hypothesized that TREM-1 and TREM-2 might be co-expressed on tumor-infiltrating myeloid cells and that elevated sTREM-1 associates with disease outcomes, thus representing a possibility for mutual modulation in cancer. Using the 4T1 breast cancer model, we found TREM-1 and TREM-2 expression on MDSC and TAM and that sTREM-1 was elevated in tumor-bearing mice in multiple models and correlated with tumor volume. While TREM-1 engagement enhanced TNF, a TREM-2 ligand was detected on MDSC and TAM, suggesting that both TREM could be functional in the tumor setting. Similarly, we detected TREM-1 and Trem2 expression in myeloid cells in the RENCA model of renal cell carcinoma (RCC). We confirmed these findings in human disease by demonstrating the expression of TREM-1 on tumor-infiltrating myeloid cells from patients with RCC and finding that sTREM-1 was increased in patients with RCC. Finally, The Cancer Genome Atlas analysis shows that TREM1 expression in tumors correlates with poor outcomes in RCC. Taken together, our data suggest that manipulation of the TREM-1/TREM-2 balance in tumors may be a novel means to modulate tumor-infiltrating myeloid cell phenotype and function. Frontiers Media S.A. 2022-02-10 /pmc/articles/PMC8867210/ /pubmed/35223446 http://dx.doi.org/10.3389/fonc.2021.662723 Text en Copyright © 2021 Ford, Gonzalez-Cotto, MacFarlane, Peri, Howard, Subleski, Ruth, Haseebuddin, Al-Saleem, Yang, Rayman, Rini, Linehan, Finke, Weiss, Campbell and McVicar https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Ford, Jill W. Gonzalez-Cotto, Marieli MacFarlane, Alexander W. Peri, Suraj Howard, O. M. Zack Subleski, Jeffrey J. Ruth, Karen J. Haseebuddin, Mohammed Al-Saleem, Tahseen Yang, Youfeng Rayman, Pat Rini, Brian Linehan, W. Marston Finke, James Weiss, Jonathan M. Campbell, Kerry S. McVicar, Daniel W. Tumor-Infiltrating Myeloid Cells Co-Express TREM1 and TREM2 and Elevated TREM-1 Associates With Disease Progression in Renal Cell Carcinoma |
title | Tumor-Infiltrating Myeloid Cells Co-Express TREM1 and TREM2 and Elevated TREM-1 Associates With Disease Progression in Renal Cell Carcinoma |
title_full | Tumor-Infiltrating Myeloid Cells Co-Express TREM1 and TREM2 and Elevated TREM-1 Associates With Disease Progression in Renal Cell Carcinoma |
title_fullStr | Tumor-Infiltrating Myeloid Cells Co-Express TREM1 and TREM2 and Elevated TREM-1 Associates With Disease Progression in Renal Cell Carcinoma |
title_full_unstemmed | Tumor-Infiltrating Myeloid Cells Co-Express TREM1 and TREM2 and Elevated TREM-1 Associates With Disease Progression in Renal Cell Carcinoma |
title_short | Tumor-Infiltrating Myeloid Cells Co-Express TREM1 and TREM2 and Elevated TREM-1 Associates With Disease Progression in Renal Cell Carcinoma |
title_sort | tumor-infiltrating myeloid cells co-express trem1 and trem2 and elevated trem-1 associates with disease progression in renal cell carcinoma |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8867210/ https://www.ncbi.nlm.nih.gov/pubmed/35223446 http://dx.doi.org/10.3389/fonc.2021.662723 |
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