Journal
CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 70, Issue 11, Pages 3235-3248Publisher
SPRINGER
DOI: 10.1007/s00262-021-02931-6
Keywords
CMTM6; M2 macrophage; PD-L1; Colorectal cancer; Immunotherapy
Categories
Funding
- National key R&D program of China [2017YFC1309002]
- National Basic Research Program of China (973 Program) [2015CB554002]
- National Natural Science Foundation of China [81672821, 81472313, 81773101, 81272759, 81401927, 81302151, 81802306]
- China Postdoctoral Science Foundation [2018M633081, 2018M633079]
- Natural Science Foundation of Guangdong Province [2018A030310457]
Ask authors/readers for more resources
Immunohistochemistry analysis showed that CMTM6 and PD-L1 were significantly higher in dMMR CRC patients than in pMMR CRC patients. CMTM6 expression in M2 macrophages was identified as the best biomarker for predicting the responsiveness to PD-1/PD-L1 inhibitors.
Background CMTM6 is a novel key regulator of PD-L1. High expression of both CMTM6 and PD-L1 may predict the benefit of PD-1 axis blockade in lung cancer. We aimed to investigate the expression pattern of CMTM6 between mismatch repair-defective (dMMR) and mismatch repair-proficient (pMMR) colorectal cancer (CRC) tissues and assess its correlation with the response to PD-1/PD-L1 pathway blockade. Methods Immunohistochemistry (IHC) was used to analyze CMTM6 and PD-L1 expression and immune cell density in dMMR/pMMR CRC. Quantitative multiplex immunofluorescence (IF) was performed to detect CMTM6, PD-L1, CD4, CD8, CD68 and CD163 expression in CRC patients treated with PD-1/PD-L1 inhibitors. Result IHC analysis showed that CMTM6 and PD-L1 were both expressed in tumor cells (TCs) and invasion front immune cells (ICs). CMTM6 and PD-L1 expression and CD4(+), CD8(+), CD68(+) or CD163(+) cell density were significantly higher in dMMR CRC patients than in pMMR CRC patients. CMTM6 expression was positively correlated with PD-L1 expression and CD163(+) M2 macrophage density in dMMR CRC. IF analysis showed that the coexpression rate of CMTM6/PD-L1 and the expression rate of CMTM6 in CD8(+) T cells and CD163(+) M2 macrophages were significantly increased in the group that exhibited clinical benefit. CMTM6 expression in M2 macrophages was identified as the best biomarker for predicting the responsiveness to PD-1/PD-L1 inhibitors. Conclusions CMTM6 expression in M2 macrophages may predict the PD-1/PD-L1 inhibitor response rate in CRC patients more accurately than dMMR/microsatellite instability-high (MSI-H) status. It can also identify pMMR CRC patients who could benefit from PD-1/PD-L1 inhibitors.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available