DNA mismatch repair deficiency (MMRd) is associated with elevated tumor mutational burden (TMB) and exceptional immunotherapy responses, yet some patients experience no clinical benefit. Recent work proposes that high intra-tumoral heterogeneity can offset immunogenicity in sporadic MMRd, suggesting a potential mechanism of immunotherapy failure.
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Reading, J.L., Caswell, D.R. & Swanton, C. Tumor heterogeneity impairs immunogenicity in mismatch repair deficient tumors. Nat Genet 55, 1610–1612 (2023). https://doi.org/10.1038/s41588-023-01492-x
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DOI: https://doi.org/10.1038/s41588-023-01492-x
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