Improving the efficiency of immune checkpoint inhibitors for metastatic pMMR/MSS colorectal cancer: Options and strategies.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and been extensively used for patients with metastastic colorectal cancer (mCRC), especially those harboring deficient mismatch repair/ microsatellite instability (dMMR/MSI). However, the majority of mCRC are classified as proficient mismatch repair/microsatellite stability(pMMR/MSS) type characterized by a cold immune microenvironment, rendering them generally unresponsive to ICIs. How to improve the efficacy of ICIs for these patients is an important issue to be solved. On the one hand, it is urgent to discover the predictive biomarkers and clinical characteristics associated with effectiveness and expand the subset of pMMR/MSS mCRC patients who benefit from ICIs. Additionally, combined strategies are being explored to modulate the immune microenvironment of pMMR/MSS CRC and facilitate the conversion of cold tumors into hot tumors. In this review, we have focused on the recent advancements in the predictive biomarkers and combination therapeutic strategies with ICIs for pMMR/MSS mCRC. [Display omitted] • ICIs have enduring advantages for dMMR/MSI mCRC. However, the resistance to ICIs among the pMMR/MSS subgroup is prevalent. • The identification of predictive biomarkers and exploration of combined strategies carry significant implications. • The identification of novel biomarkers for predicting efficacy holds promise for expanding the beneficiaries. • The combined strategies aimed at transforming "cold" tumors into "hot" tumors will generate new prospects for pMMR/MMS CRC. [ABSTRACT FROM AUTHOR]