The role of immune checkpoint inhibitors for patients with advanced stage microsatellite stable colorectal cancer and high tumor mutation burden: quantity or quality?

Patients with microsatellite stable CRC with TMB ≥ 10 without POLE and POLD1 mutations may not benefit significantly from immune checkpoint inhibitors therapy. Predetermined cutoff TMB ≥ 10 mutation per MB does not seem to define a universal cutoff for the benefit of disease-agnostic ICI therapy, particularly for patients with MSS CRC. Patients with POLE/POLD1 mutations with MSS CRC represent a unique biological subgroup of MSS CRC with favorable responses to ICI therapy.