Inducing Hypermutability to Promote Anti–PD-1 Therapy Response

Summary: The lack of clinical activity from various immune-checkpoint blockade approaches in mismatch repair– proficient (MMRp) colorectal cancer has demonstrated a critical need for novel approaches. In this issue, Crisafulli and colleagues provide proof of concept for the induction of hypermutability through the use of temozolomide as a potential pathway for enabling a productive anti–PD-1 immune response in MMRp colorectal cancer. See related article by Crisafulli et al., p. 1656 (1) .