The Impact of Tumor Heterogeneity on Immunogenicity in Mismatch Repair Deficient Tumors

Tumor heterogeneity can impair immunogenicity in mismatch repair deficient (MMRd) tumors, potentially leading to immunotherapy failure. While high tumor mutational burden (TMB) is associated with exceptional immunotherapy responses, some MMRd patients do not experience clinical benefit. Recent research suggests that high intra-tumoral heterogeneity can offset immunogenicity in sporadic MMRd tumors, highlighting the need for further investigation into the mechanisms underlying immunotherapy resistance.