Limited evidence of tumour mutational burden as a biomarker of response to immunotherapy

@article{Gurjao2020LimitedEO,
  title={Limited evidence of tumour mutational burden as a biomarker of response to immunotherapy},
  author={Carino Gurjao and Dina I Tsukrov and Maxim Imakaev and Lovelace J. Luquette and Leonid A. Mirny},
  journal={bioRxiv},
  year={2020}
}
Cancer immunotherapy by immune checkpoint blockade (ICB) is effective for several cancer types 1, however, its clinical use is encumbered by a high variability in patient response. Several studies have suggested that Tumour Mutational Burden (TMB) correlates with patient response to ICB treatments 2–6, likely due to immunogenic neoantigens generated by novel mutations accumulated during cancer progression 7. Association of TMB and response to checkpoint inhibitors has become widespread in the… 

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Mismatch repair deficiency is not sufficient to increase tumor immunogenicity

It is demonstrated that immunosurveillance in MMRd tumors has no impact on TMB but shapes the clonal architecture of neoantigens by exacerbating ITH, which provides important context for understanding immune evasion in cancers with high TMB and have major implications for therapies aimed at increasing TMB.

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Archetypes of checkpoint-responsive immunity.

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