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

Shou-Sheng Liu,Qiong Yang,Bei Zhang,Xiao-Jun Xia,Yuan-Zhong Yang,Chang Jiang,Liang-Ping Xia,Yu-Ming Rong,Ping Chen,Wen-Zhuo He,Peng-Fei Kong,Lin Yang,Qian-Kun Xie,Xiao-Pai Wang,Qi Quan

doi:10.1186/s12967-018-1570-z

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.

Highlights

Mismatch repair-deficient status is a promising candidate for targeted immune checkpoint inhibition therapy in colorectal cancer (CRC) patients, the potential immunological mechanism has not yet been well clarified and some other predictors need to be excavated as well
Anti-programmed death-1 (PD-1) therapy has not shown encouraging outcomes in colorectal cancer (CRC) until 2015, when a phase II study showed that 40% of mismatch repair-deficient CRC patients achieved an objective response, while none of the patients with mismatch repair-proficient status responded to anti-PD-1 therapy [4]
Differentiated adenocarcinoma accounted for 56.4%, while well-differentiated adenocarcinoma made up only 0.9% of all pathological types

Summary

Introduction

Mismatch repair-deficient (dMMR) status is a promising candidate for targeted immune checkpoint inhibition therapy in colorectal cancer (CRC) patients, the potential immunological mechanism has not yet been well clarified and some other predictors need to be excavated as well. Anti-PD-1 therapy has not shown encouraging outcomes in colorectal cancer (CRC) until 2015, when a phase II study showed that 40% of mismatch repair-deficient (dMMR) CRC patients achieved an objective response, while none of the patients with mismatch repair-proficient (pMMR) status responded to anti-PD-1 therapy [4]. DMMR CRC patients are suggested to be promising candidates for targeted immune checkpoint inhibition therapy. The most mentioned explanation for the enhanced activity of anti-PD-1 therapy in dMMR patients is the generation of neo-antigens, which activate T cell response to tumor cells [4, 5]. As only less than half dMMR CRC patients benefit from anti-PD-1 therapy, MMR status might not be the only positive predictor for antiPD-1 therapy, some other predictive indexes should be explored to combine with MMR status in order to better predict the curative effect

Methods

Results

Discussion

Conclusion