Immune Checkpoint Therapy and the Search for Predictive Biomarkers

Abstract

Immune checkpoint therapy has started a revolution in the field of oncology. The concept that the immune system plays a critical role in antitumor responses, which has been around for decades, has finally been proven and firmly established with elegant preclinical studies and dramatic clinical responses in patients as a result of antibodies that block inhibitory T-cell pathways. However, the clinical responses being achieved are only in a subset of patients, and more work is needed to provide a better understanding of the mechanisms that elicit tumor rejection, which will enable identification of appropriate biomarkers, reveal new targets, provide data to guide combination studies, and eventually dictate a platform that allows more patients to derive clinical benefit, including cures, with immune checkpoint therapy.

Figure 1

Depiction of “reverse translation” whereby we start by conducting immunotherapy clinical trials in patients to obtain appropriate tumor tissues and blood samples for exploratory studies, which enables hypothesis generation and subsequent experiments in animal models for hypothesis testing, with data from both the patients and animals providing a greater understanding and leading to development of more effective therapies.