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Pan-tumor genomic biomarkers for personalization of PD-1 checkpoint blockade based immunotherapy

ABSTRACT: Pan-tumor genomic biomarkers for personalization of PD-1 checkpoint blockade based immunotherapy

PROVIDER: PRJNA449580 | ENA |

REPOSITORIES: ENA

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Pan-tumor genomic biomarkers for personalization of PD-1 checkpoint blockade based immunotherapy

Project description:Pan-tumor genomic biomarkers for personalization of PD-1 checkpoint blockade based immunotherapy

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Checkpoint Blockade Cancer Immunotherapy Targets Tumor-Specific Mutant Antigens

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Project description:Programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) checkpoint blockade immunotherapy elicits durable antitumor effects in multiple cancers, yet not all patients respond. We report the evaluation of >300 patient samples across 22 tumor types from four KEYNOTE clinical trials. Tumor mutational burden (TMB) and a T cell-inflamed gene expression profile (GEP) exhibited joint predictive utility in identifying responders and nonresponders to the PD-1 antibody pembrolizumab. TMB and GEP were independently predictive of response and demonstrated low correlation, suggesting that they capture distinct features of neoantigenicity and T cell activation. Analysis of The Cancer Genome Atlas database showed TMB and GEP to have a low correlation, and analysis by joint stratification revealed biomarker-defined patterns of targetable-resistance biology. These biomarkers may have utility in clinical trial design by guiding rational selection of anti-PD-1 monotherapy and combination immunotherapy regimens.

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