The degree of microsatellite instability predicts response to PD-1 blockade immunotherapy in mismatch repair-deficient/microsatellite instability-high colorectal cancers

• Main Authors: Qiao-Xuan Wang, Chun-Hua Qu, Yuan-Hong Gao, Pei-Rong Ding, Jing-Ping Yun, Dan Xie, Mu-Yan Cai
• Format: Article
• Language: English
• Published: BMC 2021-01-01
• Series: Experimental Hematology & Oncology
• Subjects: dMMR/MSI-H; Anti-PD-1 immunotherapy; Colorectal cancer
• Online Access: https://doi.org/10.1186/s40164-020-00193-z

Abstract The development of programmed cell death-1 inhibitor (PD-1) has shed light on the treatment of tumors with deficiencies in DNA mismatch repair system or microsatellite instability (dMMR/MSI). However, predicting the subset in this group that will benefit from PD-1 blockade remains a challenge. In this study, we aimed to investigate the relationship between the degree of microsatellite instability and the responses to anti-PD-1 immunotherapy. 33 patients with colorectal adenocarcinoma who had a known MSI status and received anti-PD-1 immunotherapy were included. PCR results for MSI of the whole cohort were collected and treatment response was evaluated. Our data indicated that objective response rate (ORR) in instability-high group (instability loci ≥ 3) was significantly higher than ORR in instability-intermediate group (13/16 versus 6/17, P = 0.008). Besides, patients in instability-high group had significant longer progression-free survival (log-rank test, P = 0.004), and a significant increase in T lymphocyte infiltration and cytolytic activity in tumors. Future study might implement the intensity of microsatellite instability for more delicate selection for anti-PD-1 therapy in patient with dMMR/MSI-H tumors.