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Clever-1 positive macrophages in breast cancer

PURPOSE: Common Lymphatic Endothelial and Vascular Endothelial Receptor 1 (Clever-1) is expressed by a subset of immunosuppressive macrophages and targeting the receptor with therapeutic antibodies has been shown to activate T-cell-mediated anti-cancer immunity. The aim of this research was to study...

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Autores principales: Mutka, Minna, Virtakoivu, Reetta, Joensuu, Kristiina, Hollmén, Maija, Heikkilä, Päivi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9464734/
https://www.ncbi.nlm.nih.gov/pubmed/35917053
http://dx.doi.org/10.1007/s10549-022-06683-4
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author Mutka, Minna
Virtakoivu, Reetta
Joensuu, Kristiina
Hollmén, Maija
Heikkilä, Päivi
author_facet Mutka, Minna
Virtakoivu, Reetta
Joensuu, Kristiina
Hollmén, Maija
Heikkilä, Päivi
author_sort Mutka, Minna
collection PubMed
description PURPOSE: Common Lymphatic Endothelial and Vascular Endothelial Receptor 1 (Clever-1) is expressed by a subset of immunosuppressive macrophages and targeting the receptor with therapeutic antibodies has been shown to activate T-cell-mediated anti-cancer immunity. The aim of this research was to study Clever-1 expression in breast cancer. Specifically, how Clever-1 + macrophages correlate with clinicopathologic factors, Tumor Infiltrating Lymphocytes (TILs) and prognosis. METHODS: Tissue microarray blocks were made from 373 primary breast cancer operation specimens. Hematoxylin and Eosin (H&E-staining) and immunohistochemical staining with Clever-1, CD3, CD4 and CD8 antibodies were performed. Differences in quantities of Clever-1 + macrophages and TILs were analyzed. Clever-1 + cell numbers were correlated with 25-year follow-up survival data and with breast cancer clinicopathologic parameters. RESULTS: Low numbers of intratumoral Clever-1 + cells were found to be an independent adverse prognostic sign. Increased numbers of Clever-1 + cells were found in high grade tumors and hormone receptor negative tumors. Tumors that had higher amounts of Clever-1 + cells also tended to have higher amounts of TILs. CONCLUSION: The association of intratumoral Clever-1 + macrophages with better prognosis might stem from the function of Clever as a scavenger receptor that modulates tumor stroma. The association of Clever-1 + macrophages with high number of TILs and better prognosis indicates that immunosuppression by M2 macrophages is not necessarily dampening adaptive immune responses but instead keeping them in control to avoid excess inflammation.
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spelling pubmed-94647342022-09-13 Clever-1 positive macrophages in breast cancer Mutka, Minna Virtakoivu, Reetta Joensuu, Kristiina Hollmén, Maija Heikkilä, Päivi Breast Cancer Res Treat Preclinical Study PURPOSE: Common Lymphatic Endothelial and Vascular Endothelial Receptor 1 (Clever-1) is expressed by a subset of immunosuppressive macrophages and targeting the receptor with therapeutic antibodies has been shown to activate T-cell-mediated anti-cancer immunity. The aim of this research was to study Clever-1 expression in breast cancer. Specifically, how Clever-1 + macrophages correlate with clinicopathologic factors, Tumor Infiltrating Lymphocytes (TILs) and prognosis. METHODS: Tissue microarray blocks were made from 373 primary breast cancer operation specimens. Hematoxylin and Eosin (H&E-staining) and immunohistochemical staining with Clever-1, CD3, CD4 and CD8 antibodies were performed. Differences in quantities of Clever-1 + macrophages and TILs were analyzed. Clever-1 + cell numbers were correlated with 25-year follow-up survival data and with breast cancer clinicopathologic parameters. RESULTS: Low numbers of intratumoral Clever-1 + cells were found to be an independent adverse prognostic sign. Increased numbers of Clever-1 + cells were found in high grade tumors and hormone receptor negative tumors. Tumors that had higher amounts of Clever-1 + cells also tended to have higher amounts of TILs. CONCLUSION: The association of intratumoral Clever-1 + macrophages with better prognosis might stem from the function of Clever as a scavenger receptor that modulates tumor stroma. The association of Clever-1 + macrophages with high number of TILs and better prognosis indicates that immunosuppression by M2 macrophages is not necessarily dampening adaptive immune responses but instead keeping them in control to avoid excess inflammation. Springer US 2022-08-02 2022 /pmc/articles/PMC9464734/ /pubmed/35917053 http://dx.doi.org/10.1007/s10549-022-06683-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Preclinical Study
Mutka, Minna
Virtakoivu, Reetta
Joensuu, Kristiina
Hollmén, Maija
Heikkilä, Päivi
Clever-1 positive macrophages in breast cancer
title Clever-1 positive macrophages in breast cancer
title_full Clever-1 positive macrophages in breast cancer
title_fullStr Clever-1 positive macrophages in breast cancer
title_full_unstemmed Clever-1 positive macrophages in breast cancer
title_short Clever-1 positive macrophages in breast cancer
title_sort clever-1 positive macrophages in breast cancer
topic Preclinical Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9464734/
https://www.ncbi.nlm.nih.gov/pubmed/35917053
http://dx.doi.org/10.1007/s10549-022-06683-4
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