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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Bibliographic Details
Published in:Cancers 2021, Vol.13 (21), p.5545
Main Authors: Mezheyeuski, Artur, Micke, Patrick, Martín-Bernabé, Alfonso, Backman, Max, Hrynchyk, Ina, Hammarström, Klara, Ström, Simon, Ekström, Joakim, Edqvist, Per-Henrik, Sundström, Magnus, Ponten, Fredrik, Leandersson, Karin, Glimelius, Bengt, Sjöblom, Tobias
Format: Article
Language:English
Subjects:
Cancer and Oncology
Cancer och onkologi
Cancer therapies
CD3 antigen
CD4 antigen
CD8 antigen
Chemotherapy
Classification
Clinical Medicine
Colon cancer
Colorectal cancer
Colorectal carcinoma
Dendritic cells
Flow cytometry
Gene expression
Image processing
Immune landscape
Immunofluorescence
Inflammation
Innate immunity
Invasiveness
Klinisk medicin
Lymphocytes T
Macrophages
Medical and Health Sciences
Medical prognosis
Medicin och hälsovetenskap
Metastases
Microenvironments
Multiplex
Mutation
Pathology
Patients
Patologi
Software
Stroma
Surgery
Tumor immunology
Tumors
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Summary: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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13215545