Comparison of immunological characteristics between paired mismatch repair-proficient and -deficient colorectal cancer patients

• Published in: Journal of translational medicine Vol. 16; no. 1; p. 195
• Main Authors: Liu, Shou-Sheng, Yang, Yuan-Zhong, Jiang, Chang, Quan, Qi, Xie, Qian-Kun, Wang, Xiao-Pai, He, Wen-Zhuo, Rong, Yu-Ming, Chen, Ping, Yang, Qiong, Yang, Lin, Zhang, Bei, Xia, Xiao-Jun, Kong, Peng-Fei, Xia, Liang-Ping
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 13-07-2018; BioMed Central; BMC
• Subjects: Analysis; Antigens; Cancer patients; Care and treatment; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - immunology; Colorectal Neoplasms - pathology; Comparative analysis; Diagnosis; DNA mismatch repair; DNA Mismatch Repair - immunology; Female; Health aspects; Histocompatibility Antigens Class I - metabolism; Humans; Immunology; Inhibition (Neurophysiology); Investigations; Ligands; Logistic Models; Male; Medical prognosis; Melanoma; MHC class I molecules; Middle Aged; Mismatch repair; Mismatch repair-deficient; Mismatch repair-proficient; Multivariate analysis; Mutation; PD-L1 protein; Programmed death-1; Risk Factors; Tumors; Mismatch repair-deficient; Colorectal cancer; Mismatch repair-proficient; MHC class I molecules; Programmed death-1
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-018-1570-z

Currently, mismatch repair-deficient (dMMR) status is a promising candidate for targeted immune checkpoint inhibition therapy in colorectal cancer (CRC) patients, however, the potential immunological mechanism has not yet been well clarified and some other predictors need to be excavated as well.
We collected 330 CRC patients by the match of mismatch repair-proficient (167) and dMMR (163), explored the relationship between MMR status and some important immune molecules including MHC class I, CD3, CD4, CD8, CD56, programmed death-1 and programmed death ligand-1, and investigated the risk factors for dMMR status as well as low MHC class I expression. The Pearson Chi square test was used for analyzing the associations between clinicopathological and immune characteristics and MMR status, and two categories logistic regression model was used for univariate and multivariate analysis to predict the odds ratio of risk factors for dMMR status and low MHC class I expression.
Multivariate logistic regression analysis showed that low MHC class I and CD4 expression and high CD8 expression were significant risk factors for dMMR status [odds ratio (OR) = 24.66, 2.94 and 2.97, respectively; all p < 0.05] and dMMR status was the only risk factor for low MHC class I expression (OR = 15.34; p < 0.001).
High CD8 and low MHC class I expression suggests the contradiction and complexity of immune microenvironment in dMMR CRC patients. Some other immunocytes such as CD56
cells might also participate in the process of immune checkpoint inhibition, whereas needs further investigations.