Arid
DOI10.3390/cancers13215545
The Immune Landscape of Colorectal Cancer
Mezheyeuski, Artur; Micke, Patrick; Martin-Bernabe, Alfonso; Backman, Max; Hrynchyk, Ina; Hammarstrom, Klara; Strom, Simon; Ekstrom, Joakim; Edqvist, Per-Henrik; Sundstrom, Magnus; Ponten, Fredrik; Leandersson, Karin; Glimelius, Bengt; Sjoblom, Tobias
通讯作者Mezheyeuski, A (corresponding author), Uppsala Univ, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden.
来源期刊CANCERS
EISSN2072-6694
出版年2021
卷号13期号:21
英文摘要Simple Summary:& nbsp;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.
英文关键词colorectal cancer multiplex tumor immunology immune landscape
类型Article
语种英语
开放获取类型gold, Green Published
收录类别SCI-E
WOS记录号WOS:000720754300001
WOS关键词MICROSATELLITE INSTABILITY ; LYMPHOCYTES ; NIVOLUMAB ; TUMORS ; CELLS ; COLON
WOS类目Oncology
WOS研究方向Oncology
资源类型期刊论文
条目标识符http://119.78.100.177/qdio/handle/2XILL650/373818
作者单位[Mezheyeuski, Artur; Micke, Patrick; Backman, Max; Hammarstrom, Klara; Strom, Simon; Ekstrom, Joakim; Edqvist, Per-Henrik; Sundstrom, Magnus; Ponten, Fredrik; Glimelius, Bengt; Sjoblom, Tobias] Uppsala Univ, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden; [Martin-Bernabe, Alfonso] Karolinska Inst, Canc Ctr Karolinska, Dept Oncolpathol, S-17164 Stockholm, Sweden; [Hrynchyk, Ina] City Clin Pathologoanat Bur, Minsk 220116, BELARUS; [Leandersson, Karin] Lund Univ, Dept Translat Med, S-20502 Malmo, Sweden
推荐引用方式
GB/T 7714
Mezheyeuski, Artur,Micke, Patrick,Martin-Bernabe, Alfonso,et al. The Immune Landscape of Colorectal Cancer[J],2021,13(21).
APA Mezheyeuski, Artur.,Micke, Patrick.,Martin-Bernabe, Alfonso.,Backman, Max.,Hrynchyk, Ina.,...&Sjoblom, Tobias.(2021).The Immune Landscape of Colorectal Cancer.CANCERS,13(21).
MLA Mezheyeuski, Artur,et al."The Immune Landscape of Colorectal Cancer".CANCERS 13.21(2021).
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