Science 362, eaar3593 (2018).

In combination, tumor mutational burden and the immunological state of the tumor microenvironment predict clinical responses to programmed death–1 (PD-1) inhibition across tumor types.

Immune checkpoint–blocking antibodies have yielded unprecedented antitumor responses in patients; however this treatment is not effective in all patients, and biomarkers that predict clinical efficacy are lacking.

Razvan Cristescu et al. perform analyses of clinical samples from patients collectively diagnosed with 22 different tumor types who were enrolled in trials assessing the effect of the anti-PD-1 antibody pembrolizumab in patients with cancer. The combination of high tumor mutational burden and a gene expression program reflecting T cell activation predict the highest rates of response to PD-1 blockade.

This study provides clinically relevant biomarkers for predicting response to cancer immunotherapy.