The Immune Landscape of Colorectal Cancer

While the clinical importance of CD8+ and CD3+ cells in colorectal cancer (CRC) is well established, the impact of other immune cell subsets is less well described. We sought to provide a detailed overview of the immune landscape of CRC in the largest study to date in terms of patient numbers and in...

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Autores principales:	Artur Mezheyeuski, Patrick Micke, Alfonso Martín-Bernabé, Max Backman, Ina Hrynchyk, Klara Hammarström, Simon Ström, Joakim Ekström, Per-Henrik Edqvist, Magnus Sundström, Fredrik Ponten, Karin Leandersson, Bengt Glimelius, Tobias Sjöblom
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	colorectal cancer multiplex tumor immunology immune landscape Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/aa7f515e58784ff3830be91b167a84e4
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id	oai:doaj.org-article:aa7f515e58784ff3830be91b167a84e4
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spelling	oai:doaj.org-article:aa7f515e58784ff3830be91b167a84e42021-11-11T15:34:27ZThe Immune Landscape of Colorectal Cancer10.3390/cancers132155452072-6694https://doaj.org/article/aa7f515e58784ff3830be91b167a84e42021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5545https://doaj.org/toc/2072-6694While the clinical importance of CD8+ and CD3+ cells in colorectal cancer (CRC) is well established, the impact of other immune cell subsets is less well described. We sought to provide a detailed overview of the immune landscape of CRC in the largest study to date in terms of patient numbers and in situ analyzed immune cell types. Tissue microarrays from 536 patients were stained using multiplexed immunofluorescence panels, and fifteen immune cell subclasses, representing adaptive and innate immunity, were analyzed. Overall, therapy-naïve CRC patients clustered into an ‘inflamed’ and a ‘desert’ group. Most T cell subsets and M2 macrophages were enriched in the right colon (<i>p</i>-values 0.046–0.004), while pDC cells were in the rectum (<i>p</i> = 0.008). Elderly patients had higher infiltration of M2 macrophages (<i>p</i> = 0.024). CD8+ cells were linked to improved survival in colon cancer stages I-III (q = 0.014), while CD4+ cells had the strongest impact on overall survival in metastatic CRC (q = 0.031). Finally, we demonstrated repopulation of the immune infiltrate in rectal tumors post radiation, following an initial radiation-induced depletion. This study provides a detailed analysis of the in situ immune landscape of CRC paving the way for better diagnostics and providing hints to better target the immune microenvironment.Artur MezheyeuskiPatrick MickeAlfonso Martín-BernabéMax BackmanIna HrynchykKlara HammarströmSimon StrömJoakim EkströmPer-Henrik EdqvistMagnus SundströmFredrik PontenKarin LeanderssonBengt GlimeliusTobias SjöblomMDPI AGarticlecolorectal cancermultiplextumor immunologyimmune landscapeNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5545, p 5545 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	colorectal cancer multiplex tumor immunology immune landscape Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	colorectal cancer multiplex tumor immunology immune landscape Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Artur Mezheyeuski Patrick Micke Alfonso Martín-Bernabé Max Backman Ina Hrynchyk Klara Hammarström Simon Ström Joakim Ekström Per-Henrik Edqvist Magnus Sundström Fredrik Ponten Karin Leandersson Bengt Glimelius Tobias Sjöblom The Immune Landscape of Colorectal Cancer
description	While the clinical importance of CD8+ and CD3+ cells in colorectal cancer (CRC) is well established, the impact of other immune cell subsets is less well described. We sought to provide a detailed overview of the immune landscape of CRC in the largest study to date in terms of patient numbers and in situ analyzed immune cell types. Tissue microarrays from 536 patients were stained using multiplexed immunofluorescence panels, and fifteen immune cell subclasses, representing adaptive and innate immunity, were analyzed. Overall, therapy-naïve CRC patients clustered into an ‘inflamed’ and a ‘desert’ group. Most T cell subsets and M2 macrophages were enriched in the right colon (<i>p</i>-values 0.046–0.004), while pDC cells were in the rectum (<i>p</i> = 0.008). Elderly patients had higher infiltration of M2 macrophages (<i>p</i> = 0.024). CD8+ cells were linked to improved survival in colon cancer stages I-III (q = 0.014), while CD4+ cells had the strongest impact on overall survival in metastatic CRC (q = 0.031). Finally, we demonstrated repopulation of the immune infiltrate in rectal tumors post radiation, following an initial radiation-induced depletion. This study provides a detailed analysis of the in situ immune landscape of CRC paving the way for better diagnostics and providing hints to better target the immune microenvironment.
format	article
author	Artur Mezheyeuski Patrick Micke Alfonso Martín-Bernabé Max Backman Ina Hrynchyk Klara Hammarström Simon Ström Joakim Ekström Per-Henrik Edqvist Magnus Sundström Fredrik Ponten Karin Leandersson Bengt Glimelius Tobias Sjöblom
author_facet	Artur Mezheyeuski Patrick Micke Alfonso Martín-Bernabé Max Backman Ina Hrynchyk Klara Hammarström Simon Ström Joakim Ekström Per-Henrik Edqvist Magnus Sundström Fredrik Ponten Karin Leandersson Bengt Glimelius Tobias Sjöblom
author_sort	Artur Mezheyeuski
title	The Immune Landscape of Colorectal Cancer
title_short	The Immune Landscape of Colorectal Cancer
title_full	The Immune Landscape of Colorectal Cancer
title_fullStr	The Immune Landscape of Colorectal Cancer
title_full_unstemmed	The Immune Landscape of Colorectal Cancer
title_sort	immune landscape of colorectal cancer
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/aa7f515e58784ff3830be91b167a84e4
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The Immune Landscape of Colorectal Cancer

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