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Pre-treatment tumor-infiltrating T cells influence response to neoadjuvant chemoradiotherapy in esophageal adenocarcinoma
Esophageal adenocarcinoma (EAC) is a disease with dismal treatment outcomes. Response to neoadjuvant chemoradiation (CRT) varies greatly. Although the underlying mechanisms of CRT resistance are not identified, accumulating evidence indicates an important role for local antitumor immunity. To explor...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344794/ https://www.ncbi.nlm.nih.gov/pubmed/34377591 http://dx.doi.org/10.1080/2162402X.2021.1954807 |
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author | Goedegebuure, R.S.A. Harrasser, M. de Klerk, L.K. van Schooten, T.S. van Grieken, N.C.T. Eken, M. Grifhorst, M.S. Pocorni, N. Jordanova, E.S. van Berge Henegouwen, M.I. Pouw, R.E. Verheul, H.M.W. van der Vliet, J.J. van Laarhoven, H.W.M. Thijssen, V.L.J.L Bass, A.J. De Gruijl, T.D. Derks, S. |
author_facet | Goedegebuure, R.S.A. Harrasser, M. de Klerk, L.K. van Schooten, T.S. van Grieken, N.C.T. Eken, M. Grifhorst, M.S. Pocorni, N. Jordanova, E.S. van Berge Henegouwen, M.I. Pouw, R.E. Verheul, H.M.W. van der Vliet, J.J. van Laarhoven, H.W.M. Thijssen, V.L.J.L Bass, A.J. De Gruijl, T.D. Derks, S. |
author_sort | Goedegebuure, R.S.A. |
collection | PubMed |
description | Esophageal adenocarcinoma (EAC) is a disease with dismal treatment outcomes. Response to neoadjuvant chemoradiation (CRT) varies greatly. Although the underlying mechanisms of CRT resistance are not identified, accumulating evidence indicates an important role for local antitumor immunity. To explore the immune microenvironment in relation to response to CRT we performed an in-depth analysis using multiplex immunohistochemistry, flow cytometry and mRNA expression analysis (NanoString) to generate a detailed map of the immunological landscape of pretreatment biopsies as well as peripheral blood mononuclear cells (PBMCs) of EAC patients. Response to CRT was assessed by Mandard’s tumor regression grade (TRG), disease-free- and overall survival. Tumors with a complete pathological response (TRG 1) to neoadjuvant CRT had significantly higher tumor-infiltrating T cell levels compared to all other response groups (TRG 2–5). These T cells were also in closer proximity to tumor cells in complete responders compared to other response groups. Notably, immune profiles of near-complete responders (TRG 2) showed more resemblance to non-responders (TRG 3–5) than to complete responders. A high CD8:CD163 ratio in the tumor was associated with an improved disease-free survival. Gene expression analyses revealed that T cells in non-responders were Th2-skewed, while complete responders were enriched in cytotoxic immune cells. Finally, complete responders were enriched in circulating memory T cells. preexisting immune activation enhances the chance for a complete pathological response to neoadjuvant CRT. This information can potentially be used for future patient selection, but also fuels the development of immunomodulatory strategies to enhance CRT efficacy. |
format | Online Article Text |
id | pubmed-8344794 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-83447942021-08-09 Pre-treatment tumor-infiltrating T cells influence response to neoadjuvant chemoradiotherapy in esophageal adenocarcinoma Goedegebuure, R.S.A. Harrasser, M. de Klerk, L.K. van Schooten, T.S. van Grieken, N.C.T. Eken, M. Grifhorst, M.S. Pocorni, N. Jordanova, E.S. van Berge Henegouwen, M.I. Pouw, R.E. Verheul, H.M.W. van der Vliet, J.J. van Laarhoven, H.W.M. Thijssen, V.L.J.L Bass, A.J. De Gruijl, T.D. Derks, S. Oncoimmunology Original Research Esophageal adenocarcinoma (EAC) is a disease with dismal treatment outcomes. Response to neoadjuvant chemoradiation (CRT) varies greatly. Although the underlying mechanisms of CRT resistance are not identified, accumulating evidence indicates an important role for local antitumor immunity. To explore the immune microenvironment in relation to response to CRT we performed an in-depth analysis using multiplex immunohistochemistry, flow cytometry and mRNA expression analysis (NanoString) to generate a detailed map of the immunological landscape of pretreatment biopsies as well as peripheral blood mononuclear cells (PBMCs) of EAC patients. Response to CRT was assessed by Mandard’s tumor regression grade (TRG), disease-free- and overall survival. Tumors with a complete pathological response (TRG 1) to neoadjuvant CRT had significantly higher tumor-infiltrating T cell levels compared to all other response groups (TRG 2–5). These T cells were also in closer proximity to tumor cells in complete responders compared to other response groups. Notably, immune profiles of near-complete responders (TRG 2) showed more resemblance to non-responders (TRG 3–5) than to complete responders. A high CD8:CD163 ratio in the tumor was associated with an improved disease-free survival. Gene expression analyses revealed that T cells in non-responders were Th2-skewed, while complete responders were enriched in cytotoxic immune cells. Finally, complete responders were enriched in circulating memory T cells. preexisting immune activation enhances the chance for a complete pathological response to neoadjuvant CRT. This information can potentially be used for future patient selection, but also fuels the development of immunomodulatory strategies to enhance CRT efficacy. Taylor & Francis 2021-08-04 /pmc/articles/PMC8344794/ /pubmed/34377591 http://dx.doi.org/10.1080/2162402X.2021.1954807 Text en © 2021 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Goedegebuure, R.S.A. Harrasser, M. de Klerk, L.K. van Schooten, T.S. van Grieken, N.C.T. Eken, M. Grifhorst, M.S. Pocorni, N. Jordanova, E.S. van Berge Henegouwen, M.I. Pouw, R.E. Verheul, H.M.W. van der Vliet, J.J. van Laarhoven, H.W.M. Thijssen, V.L.J.L Bass, A.J. De Gruijl, T.D. Derks, S. Pre-treatment tumor-infiltrating T cells influence response to neoadjuvant chemoradiotherapy in esophageal adenocarcinoma |
title | Pre-treatment tumor-infiltrating T cells influence response to neoadjuvant chemoradiotherapy in esophageal adenocarcinoma |
title_full | Pre-treatment tumor-infiltrating T cells influence response to neoadjuvant chemoradiotherapy in esophageal adenocarcinoma |
title_fullStr | Pre-treatment tumor-infiltrating T cells influence response to neoadjuvant chemoradiotherapy in esophageal adenocarcinoma |
title_full_unstemmed | Pre-treatment tumor-infiltrating T cells influence response to neoadjuvant chemoradiotherapy in esophageal adenocarcinoma |
title_short | Pre-treatment tumor-infiltrating T cells influence response to neoadjuvant chemoradiotherapy in esophageal adenocarcinoma |
title_sort | pre-treatment tumor-infiltrating t cells influence response to neoadjuvant chemoradiotherapy in esophageal adenocarcinoma |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344794/ https://www.ncbi.nlm.nih.gov/pubmed/34377591 http://dx.doi.org/10.1080/2162402X.2021.1954807 |
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