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

Abstract

BackgroundCurrently, 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.MethodsWe 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.ResultsMultivariate 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).ConclusionsHigh 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.

Comparison of Mismatch Repair Status Between Primary and Matched Metastatic Sites in Patients With Colorectal Cancer

“…MSI-high CRC and loss of major histocompatibility complex class I (MHC-I) expression, 39 which is an activation signal for NK cells. Because MSI heterogeneity exists in primary CRC [31][32][33] and MSI-high tumor cells are more susceptible to NK cells because of loss of MHC-I, 40 it might be more difficult for MSI-high tumor cells to survive peritoneal metastasis in the same patient.…”

PD-L1/PD-1 crosstalk in colorectal cancer: are we targeting the right cells?

“…For all these cases, other features should also be taken into consideration when mechanisms for PD-L1/PD-1 crosstalk are dug into. These features include the generation of neo-antigens that then activate T-cell response to tumours, changes in signalling pathways of chemokines and cytokines expression, and the loss of MHC class I molecules in tumour cells [ 44 ]; all indicating the solid implication of TILs and TAMs. Hence, our results reinforce the suitability of either active or passive therapies [ 43 ] to restore patient immunity, e.g., M1-macrophage polarisation, together with ICBT.…”

Tumor-Infiltrating Lymphocytes in Colorectal Cancer: The Fundamental Indication and Application on Immunotherapy

“…It is noteworthy that a study of automatic image analysis on 768 colorectal cancers has identified the density of T cell subsets in neoplastic epithelial areas was positively correlated with MSI-H (39). In particular, several immunohistochemistry studies have revealed an especially high infiltration of intraepithelial activated CD8 + T cells within microsatellite instability colorectal tumors (42)(43)(44)(45). Dolcetti et al using immunohistochemistry found that there were many cytotoxic infiltrating structures in tumor epithelial cells in MSI-H patients.…”