Biomarkers in Precision Cancer Immunotherapy: Promise and Challenges.

The rapid expansion of modern cancer immunotherapeutics has led to a dramatic improvement in patient survival and sustained remission for otherwise refractory malignancies. However, a significant limitation behind these current treatment modalities is an irregularity in clinical response, which is especially pronounced among checkpoint inhibition. This unpredictability leads to significant side effects, financial costs, and health care burden, with unsatisfactory clinical benefit in the majority of treated patients. Additionally, although ongoing studies and trials investigate the use of multiple biomarkers predictive of patient response or harm, none of these are comprehensive in predicting potential benefit. This unmet need for validated biomarkers is largely secondary to a prohibitive complexity within tumor parenchyma and microenvironment, dynamic clonal and proteomic changes to therapy, heterogenous host immune defects, and varied standardization among sample preparation and reporting. Herein, we discuss current advantages of predictive biomarkers, as well as limitations in their clinical use and application. We also review future directions, ideal characteristics, and trial design needed for proper precision immuno-oncology and biomarker development.