CMTM6 expression in M2 macrophages is a potential predictor of PD-1/PD-L1 inhibitor response in colorectal cancer.

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.

CD24 and PRAME Are Novel Grading and Prognostic Indicators for Pineal Parenchymal Tumors of Intermediate Differentiation.

The pineal parenchymal tumors of intermediate differentiation (PPTIDs) are extremely rare tumor entities. They exhibit low-risk (grade II) and high-risk (grade III) malignancies, which may lead to different therapies and prognosis. However, the histological grading criteria remains elusive, and novel biomarkers may be helpful to differentiate the grade of PPTIDs. Immunohistochemical staining for CD24, PRAME, POU4F2, and HOXD13, and their clinicopathologic analyses were performed in pineal parenchymal tumors and other tumors in the pineal region. CD24 and PRAME were expressed in 9/11 (81.8%) and 8/11(72.7%) cases of PPTIDs grade III, compared with 6/18 (33.3%) and 5/18(27.8%) cases of PPTIDs grade II. The levels of CD24 and PRAME were significantly higher in PPTIDs grade III than grade II. However, there were no differences of HOXD13 and POU4F2 expression levels in PPTIDs grade II and grade III. Interestingly, high expression of CD24 and PRAME were prevalently found in high-grade tumors of the central nervous system. In addition, PPTIDs patients with high expression levels of CD24 and PRAME exhibited a significant shorter survival time. The results of PPTIDs grading by CD24 and PRAME were mostly consistent with WHO criteria, except for two cases. According to the prognostic information of patients, we found that the combination of CD24 and PRAME expression for grading PPTIDs might be more valuable than WHO criteria only. CD24 and PRAME are novel markers for grading and prognostic evaluation of PPTIDs that may be helpful to determine the therapeutic decision for PPTIDs patients.