Critical to improving the clinical efficacy and safety of checkpoint blockade is determining which patients are likely to respond. In this review, Havel and Chowell summarize the wide range of biomarkers linked to checkpoint response including tumor factors (mutation burden and heterogeneity, specific mutations, number and quality of neoantigens, PD-L1 expression), immune factors (tumor infiltration, T cell states, suppressive immune cells), and other host factors (HLA variants, the gut microbiome). They also call for a comprehensive predictive modeling system to collectively evaluate biomarkers and guide personalized care.
Checkpoint inhibitor-based immunotherapies that target cytotoxic T lymphocyte antigen 4 (CTLA4) or the programmed cell death 1 (PD1) pathway have achieved impressive success in the treatment of different cancer types. Yet, only a subset of patients derive clinical benefit. It is thus critical to understand the determinants driving response, resistance and adverse effects. In this Review, we discuss recent work demonstrating that immune checkpoint inhibitor efficacy is affected by a combination of factors involving tumour genomics, host germline genetics, PD1 ligand 1 (PDL1) levels and other features of the tumour microenvironment, as well as the gut microbiome. We focus on recently identified molecular and cellular determinants of response. A better understanding of how these variables cooperate to affect tumour-host interactions is needed to optimize the implementation of precision immunotherapy.
Author Info: (1) Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Can
Author Info: (1) Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (2) Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (3) Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. chant@mskcc.org. Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY, USA. chant@mskcc.org. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. chant@mskcc.org.
