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The immune landscape of colorectal cancer

Mezheyeuski, Artur ; Micke, Patrick ; Martín‐bernabé, Alfonso ; Backman, Max ; Hrynchyk, Ina ; Hammarström, Klara ; Ström, Simon ; Ekström, Joakim ; Edqvist, Per Henrik and Sundström, Magnus , et al. (2021) In Cancers 13(21).
Abstract

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 (p‐values 0.046–0.004), while pDC cells were in the rectum (p =... (More)

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 (p‐values 0.046–0.004), while pDC cells were in the rectum (p = 0.008). Elderly patients had higher infiltration of M2 macrophages (p = 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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Colorectal cancer, Immune landscape, Multiplex, Tumor immunology
in
Cancers
volume
13
issue
21
article number
5545
publisher
MDPI AG
external identifiers
  • scopus:85118360483
  • pmid:34771707
ISSN
2072-6694
DOI
10.3390/cancers13215545
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
id
ee6ccc35-b56e-41dc-9fd2-2521ed47a8fe
date added to LUP
2021-11-26 12:00:49
date last changed
2024-06-17 00:12:02
@article{ee6ccc35-b56e-41dc-9fd2-2521ed47a8fe,
  abstract     = {{<p>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 (p‐values 0.046–0.004), while pDC cells were in the rectum (p = 0.008). Elderly patients had higher infiltration of M2 macrophages (p = 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.</p>}},
  author       = {{Mezheyeuski, Artur and Micke, Patrick and Martín‐bernabé, Alfonso and Backman, Max and Hrynchyk, Ina and Hammarström, Klara and Ström, Simon and Ekström, Joakim and Edqvist, Per Henrik and Sundström, Magnus and Ponten, Fredrik and Leandersson, Karin and Glimelius, Bengt and Sjöblom, Tobias}},
  issn         = {{2072-6694}},
  keywords     = {{Colorectal cancer; Immune landscape; Multiplex; Tumor immunology}},
  language     = {{eng}},
  number       = {{21}},
  publisher    = {{MDPI AG}},
  series       = {{Cancers}},
  title        = {{The immune landscape of colorectal cancer}},
  url          = {{http://dx.doi.org/10.3390/cancers13215545}},
  doi          = {{10.3390/cancers13215545}},
  volume       = {{13}},
  year         = {{2021}},
}