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

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.

Source: ScienceNOW - October 11, 2018 Category: Science Authors: Cristescu, R., Mogg, R., Ayers, M., Albright, A., Murphy, E., Yearley, J., Sher, X., Liu, X. Q., Lu, H., Nebozhyn, M., Zhang, C., Lunceford, J. K., Joe, A., Cheng, J., Webber, A. L., Ibrahim, N., Plimack, E. R., Ott, P. A., Seiwert, T. Y., Ribas, A., McCl Tags: Immunology, Medicine, Diseases, Online Only r-articles Source Type: news