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  • Mezheyeuski, ArturUppsala University,Uppsala universitet,Experimentell och klinisk onkologi (author)

The Immune Landscape of Colorectal Cancer

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021-11-04
  • MDPI,2021
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-460222
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-460222URI
  • https://doi.org/10.3390/cancers13215545DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:148115558URI
  • https://lup.lub.lu.se/record/ee6ccc35-b56e-41dc-9fd2-2521ed47a8feURI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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 and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Micke, PatrickUppsala University,Uppsala universitet,Klinisk och experimentell patologi,Patrick Micke(Swepub:uu)patmi676 (author)
  • Martin-Bernabe, AlfonsoKarolinska Institute,Karolinska Institutet,Karolinska Inst, Canc Ctr Karolinska, Dept Oncolpathol, S-17164 Stockholm, Sweden. (author)
  • Backman, MaxUppsala University,Uppsala universitet,Klinisk och experimentell patologi,Patrick Micke(Swepub:uu)maxba655 (author)
  • Hrynchyk, InaCity Clin Pathologoanat Bur, Minsk 220116, BELARUS. (author)
  • Hammarström, KlaraUppsala University,Uppsala universitet,Experimentell och klinisk onkologi(Swepub:uu)klaha235 (author)
  • Ström, SimonUppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi (author)
  • Ekström, Joakim,1982-Uppsala University,Uppsala universitet,Experimentell och klinisk onkologi(Swepub:uu)joaek270 (author)
  • Edqvist, Per-Henrik DUppsala University,Uppsala universitet,Experimentell och klinisk onkologi(Swepub:uu)peedq227 (author)
  • Sundström, MagnusUppsala University,Uppsala universitet,Klinisk och experimentell patologi,Johan Botling(Swepub:uu)magnsund (author)
  • Ponten, FredrikUppsala University,Uppsala universitet,Klinisk och experimentell patologi,Fredrik Pontén(Swepub:uu)fredpont (author)
  • Leandersson, KarinLund 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(Swepub:lu)immu-kpe (author)
  • Glimelius, BengtUppsala University,Uppsala universitet,Experimentell och klinisk onkologi(Swepub:uu)bengglim (author)
  • Sjöblom, TobiasUppsala University,Uppsala universitet,Experimentell och klinisk onkologi(Swepub:uu)tobisjob (author)
  • Uppsala universitetExperimentell och klinisk onkologi (creator_code:org_t)

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  • In:Cancers: MDPI13:212072-6694

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