Overview on biomarkers for immune oncology drugs.

Although immune checkpoint inhibitors (ICIs) are widely used in clinical oncology, less than half of treated cancer patients derive benefit from this therapy. Both tumor- and host-related variables are implicated in response to ICIs. The predictive value of PD-L1 expression is confined only to several cancer types, so this molecule is not an agnostic biomarker. Highly elevated tumor mutation burden (TMB) caused either by excessive carcinogenic exposure or by a deficiency in DNA repair is a reliable indicator for ICI efficacy, as exemplified by tumors with high-level microsatellite instability (MSI-H). Other potentially relevant tumor-related characteristics include gene expression signatures, pattern of tumor infiltration by immune cells, and, perhaps, some immune-response modifying somatic mutations. Host-related factors have not yet been comprehensively considered in relevant clinical trials. Microbiome composition, markers of systemic inflammation [e.g., neutrophil-to-lymphocyte ratio (NLR)], and human leucocyte antigen (HLA) diversity may influence the efficacy of ICIs. Studies on ICI biomarkers are likely to reveal modifiable tumor or host characteristics, which can be utilized to direct the antitumor immune defense. Examples of the latter approach include tumor priming to immune therapy by cytotoxic drugs and elevation of ICI efficacy by microbiome modification.