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Meflin-positive cancer-associated fibroblasts enhance tumor response to immune checkpoint blockade
Cancer-associated fibroblasts (CAFs) are an integral component of the tumor microenvironment (TME). Most CAFs shape the TME toward an immunosuppressive milieu and attenuate the efficacy of immune checkpoint blockade (ICB) therapy. However, the detailed mechanism of how heterogeneous CAFs regulate tu...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8897596/ https://www.ncbi.nlm.nih.gov/pubmed/35236758 http://dx.doi.org/10.26508/lsa.202101230 |
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author | Miyai, Yuki Sugiyama, Daisuke Hase, Tetsunari Asai, Naoya Taki, Tetsuro Nishida, Kazuki Fukui, Takayuki Chen-Yoshikawa, Toyofumi Fengshi Kobayashi, Hiroki Mii, Shinji Shiraki, Yukihiro Hasegawa, Yoshinori Nishikawa, Hiroyoshi Ando, Yuichi Takahashi, Masahide Enomoto, Atsushi |
author_facet | Miyai, Yuki Sugiyama, Daisuke Hase, Tetsunari Asai, Naoya Taki, Tetsuro Nishida, Kazuki Fukui, Takayuki Chen-Yoshikawa, Toyofumi Fengshi Kobayashi, Hiroki Mii, Shinji Shiraki, Yukihiro Hasegawa, Yoshinori Nishikawa, Hiroyoshi Ando, Yuichi Takahashi, Masahide Enomoto, Atsushi |
author_sort | Miyai, Yuki |
collection | PubMed |
description | Cancer-associated fibroblasts (CAFs) are an integral component of the tumor microenvironment (TME). Most CAFs shape the TME toward an immunosuppressive milieu and attenuate the efficacy of immune checkpoint blockade (ICB) therapy. However, the detailed mechanism of how heterogeneous CAFs regulate tumor response to ICB therapy has not been defined. Here, we show that a recently defined CAF subset characterized by the expression of Meflin, a glycosylphosphatidylinositol-anchored protein marker of mesenchymal stromal/stem cells, is associated with survival and favorable therapeutic response to ICB monotherapy in patients with non-small cell lung cancer (NSCLC). The prevalence of Meflin-positive CAFs was positively correlated with CD4-positive T-cell infiltration and vascularization within non-small cell lung cancer tumors. Meflin deficiency and CAF-specific Meflin overexpression resulted in defective and enhanced ICB therapy responses in syngeneic tumors in mice, respectively. These findings suggest the presence of a CAF subset that promotes ICB therapy efficacy, which adds to our understanding of CAF functions and heterogeneity. |
format | Online Article Text |
id | pubmed-8897596 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-88975962022-04-06 Meflin-positive cancer-associated fibroblasts enhance tumor response to immune checkpoint blockade Miyai, Yuki Sugiyama, Daisuke Hase, Tetsunari Asai, Naoya Taki, Tetsuro Nishida, Kazuki Fukui, Takayuki Chen-Yoshikawa, Toyofumi Fengshi Kobayashi, Hiroki Mii, Shinji Shiraki, Yukihiro Hasegawa, Yoshinori Nishikawa, Hiroyoshi Ando, Yuichi Takahashi, Masahide Enomoto, Atsushi Life Sci Alliance Research Articles Cancer-associated fibroblasts (CAFs) are an integral component of the tumor microenvironment (TME). Most CAFs shape the TME toward an immunosuppressive milieu and attenuate the efficacy of immune checkpoint blockade (ICB) therapy. However, the detailed mechanism of how heterogeneous CAFs regulate tumor response to ICB therapy has not been defined. Here, we show that a recently defined CAF subset characterized by the expression of Meflin, a glycosylphosphatidylinositol-anchored protein marker of mesenchymal stromal/stem cells, is associated with survival and favorable therapeutic response to ICB monotherapy in patients with non-small cell lung cancer (NSCLC). The prevalence of Meflin-positive CAFs was positively correlated with CD4-positive T-cell infiltration and vascularization within non-small cell lung cancer tumors. Meflin deficiency and CAF-specific Meflin overexpression resulted in defective and enhanced ICB therapy responses in syngeneic tumors in mice, respectively. These findings suggest the presence of a CAF subset that promotes ICB therapy efficacy, which adds to our understanding of CAF functions and heterogeneity. Life Science Alliance LLC 2022-03-01 /pmc/articles/PMC8897596/ /pubmed/35236758 http://dx.doi.org/10.26508/lsa.202101230 Text en © 2022 Miyai et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles Miyai, Yuki Sugiyama, Daisuke Hase, Tetsunari Asai, Naoya Taki, Tetsuro Nishida, Kazuki Fukui, Takayuki Chen-Yoshikawa, Toyofumi Fengshi Kobayashi, Hiroki Mii, Shinji Shiraki, Yukihiro Hasegawa, Yoshinori Nishikawa, Hiroyoshi Ando, Yuichi Takahashi, Masahide Enomoto, Atsushi Meflin-positive cancer-associated fibroblasts enhance tumor response to immune checkpoint blockade |
title | Meflin-positive cancer-associated fibroblasts enhance tumor response to immune checkpoint blockade |
title_full | Meflin-positive cancer-associated fibroblasts enhance tumor response to immune checkpoint blockade |
title_fullStr | Meflin-positive cancer-associated fibroblasts enhance tumor response to immune checkpoint blockade |
title_full_unstemmed | Meflin-positive cancer-associated fibroblasts enhance tumor response to immune checkpoint blockade |
title_short | Meflin-positive cancer-associated fibroblasts enhance tumor response to immune checkpoint blockade |
title_sort | meflin-positive cancer-associated fibroblasts enhance tumor response to immune checkpoint blockade |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8897596/ https://www.ncbi.nlm.nih.gov/pubmed/35236758 http://dx.doi.org/10.26508/lsa.202101230 |
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