Hyperprogression: A novel response pattern under immunotherapy.

Checkpoint blockade therapy has shown significant therapeutic benefits and resulted in durable responses in patients with various tumors. However, accumulating evidence has demonstrated that 4-29% of all patients with cancers with various histologies may suffer from tumor flare following such therapy. This novel tumor response pattern, termed hyperprogression, is a potentially deleterious side effect of checkpoint blockade therapy that accelerates disease progression in a subset of patients. In this review, we describe possible immune checkpoint blockade biomarkers and the epidemiology, different definitions, and predictors of hyperprogression based on the research findings and further present the available evidence supporting pathophysiological hypotheses that might explain hyperprogression during checkpoint blockade therapy. We also compare hyperprogression and pseudoprogression. Finally, we discuss areas requiring further study.

Progress in Neoantigen Targeted Cancer Immunotherapies.

Immunotherapies that harness the immune system to kill cancer cells have showed significant therapeutic efficacy in many human malignancies. A growing number of studies have highlighted the relevance of neoantigens in recognizing cancer cells by intrinsic T cells. Cancer neoantigens are a direct consequence of somatic mutations presenting on the surface of individual cancer cells. Neoantigens are fully cancer-specific and exempt from central tolerance. In addition, neoantigens are important targets for checkpoint blockade therapy. Recently, technological innovations have made neoantigen discovery possible in a variety of malignancies, thus providing an impetus to develop novel immunotherapies that selectively enhance T cell reactivity for the destruction of cancer cells while leaving normal tissues unharmed. In this review, we aim to introduce the methods of the identification of neoantigens, the mutational patterns of human cancers, related clinical trials, neoantigen burden and sensitivity to immune checkpoint blockade. Moreover, we focus on relevant challenges of targeting neoantigens for cancer treatment.