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DOI | 10.3390/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
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EISSN | 2072-6694 |
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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