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The Immune Landscap...
The Immune Landscape of Colorectal Cancer
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- Mezheyeuski, Artur (author)
- Uppsala University,Uppsala universitet,Experimentell och klinisk onkologi
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- Micke, Patrick (author)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Patrick Micke
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- Martin-Bernabe, Alfonso (author)
- Karolinska Institute,Karolinska Institutet,Karolinska Inst, Canc Ctr Karolinska, Dept Oncolpathol, S-17164 Stockholm, Sweden.
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- Backman, Max (author)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Patrick Micke
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- Hrynchyk, Ina (author)
- City Clin Pathologoanat Bur, Minsk 220116, BELARUS.
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- Hammarström, Klara (author)
- Uppsala University,Uppsala universitet,Experimentell och klinisk onkologi
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- Ström, Simon (author)
- Uppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Ekström, Joakim, 1982- (author)
- Uppsala University,Uppsala universitet,Experimentell och klinisk onkologi
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- Edqvist, Per-Henrik D (author)
- Uppsala University,Uppsala universitet,Experimentell och klinisk onkologi
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- Sundström, Magnus (author)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Johan Botling
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- Ponten, Fredrik (author)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Fredrik Pontén
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- Leandersson, Karin (author)
- Lund University,Lunds universitet,Cancerimmunologi, Malmö,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Cancer Immunology, Malmö,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Glimelius, Bengt (author)
- Uppsala University,Uppsala universitet,Experimentell och klinisk onkologi
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- Sjöblom, Tobias (author)
- Uppsala University,Uppsala universitet,Experimentell och klinisk onkologi
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(creator_code:org_t)
- 2021-11-04
- 2021
- English.
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In: Cancers. - : MDPI. - 2072-6694. ; 13:21
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https://doi.org/10.3...
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Abstract
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- We sought to provide a detailed overview of the immune landscape of colorectal cancer in the largest study to date in terms of patient numbers and analyzed immune cell types. We applied a multiplex in situ staining method in combination with an advanced scanning and image analysis pipeline akin to flow cytometry, and analyzed 5968 individual multi-layer images of tissue defining in a total of 39,078,450 cells. We considered the location of immune cells with respect to the stroma, and tumor cell compartment and tumor regions in the central part or the invasive margin. To the best of our knowledge, this study is the first comprehensive spatial description of the immune landscape in colorectal cancer using a large population-based cohort and a multiplex immune cell identification.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-naive 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
Keyword
- colorectal cancer
- multiplex
- tumor immunology
- immune landscape
- Pathology
- Patologi
- Colorectal cancer
- Immune landscape
- Multiplex
- Tumor immunology
Publication and Content Type
- ref (subject category)
- art (subject category)
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Cancers
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Mezheyeuski, Art ...
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Micke, Patrick
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Martin-Bernabe, ...
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Backman, Max
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Hrynchyk, Ina
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Hammarström, Kla ...
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Ström, Simon
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Ekström, Joakim, ...
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Edqvist, Per-Hen ...
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Sundström, Magnu ...
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Ponten, Fredrik
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Leandersson, Kar ...
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Glimelius, Bengt
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Sjöblom, Tobias
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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- Articles in the publication
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Cancers
- By the university
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Uppsala University
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Karolinska Institutet
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Lund University