The clinical development of checkpoint inhibitor-based immunotherapy has ushered in an exciting era of anticancer therapy. Durable responses can be seen in patients with melanoma and other malignancies. Although monotherapy with PD-1 or PD-L1 agents are typically well tolerated, the risk of immune-related adverse events increases with combination regimens. The development of predictive biomarkers is needed to optimise patient benefit, minimise risk of toxicities, and guide combination approaches. The greatest focus has been on tumour-cell PD-L1 expression. Although PD-L1 positivity enriches for populations with clinical benefit, PD-L1 testing alone is insufficient for patient selection in most malignancies. In this Review, we discuss the status of PD-L1 testing and explore emerging data on new biomarker strategies with tumour-infiltrating lymphocytes, mutational burden, immune gene signatures, and multiplex immunohistochemistry. Future development of an effective predictive biomarker for checkpoint inhibitor-based immunotherapy will integrate multiple approaches for optimal characterisation of the immune tumour microenvironment.

The purpose of the National Cancer Institute (NCI) pilot project to prioritize cancer antigens was to develop a well-vetted ranked prioritized list of cancer vaccine target antigens based on pre-defined and pre-weighted objective criteria. An additional aim was for the NCI to test a new approach for prioritizing translational research opportunities based on an Analytic Hierarchy Process for dealing with complex decisions. Antigen prioritization involved developing a list of “ideal” cancer antigen criteria/characteristics, assigning relative weights to those criteria using pair-wise comparisons, selecting 75 representative antigens for comparison and ranking, assembling information on the pre-defined criteria for the selected antigens, and ranking the antigens based on the pre-defined, pre-weighted criteria. Using the pair-wise approach, the result of criteria weighting, in descending order was: (1) Therapeutic function, (2) Immunogenicity, (3) Role of the antigen in oncogenicity, (4) Specificity, (5) Expression level and percent of antigen positive cells, (6) Stem cell expression, (7) Number of patients with antigen positive cancers, (8) Number of antigenic epitopes and (9) Cellular location of antigen expression. None of the 75 antigens had all of the characteristics of the “ideal” cancer antigen. However, 46 were immunogenic in clinical trials and 20 of them had suggestive clinical efficacy in the “Therapeutic function” category. These findings reflect the current status of the cancer vaccine field, highlight the possibility that additional organized efforts and funding would accelerate the development of therapeutically effective cancer vaccines, and accentuate the need for prioritization.