Emerging biomarkers for cancer immunotherapy in melanoma

Abstract

The treatment and prognosis of metastatic melanoma has changed substantially since the advent of novel immune checkpoint inhibitors (ICI), agents that enhance the anti-tumor immune response. Despite the success of these agents, clinically actionable biomarkers to aid patient and regimen selection are lacking. Herein, we summarize and review the evidence for candidate biomarkers of response to ICIs in melanoma. Many of these candidates can be examined as parts of a known molecular pathway of immune response, while others are clinical in nature. Due to the ability of ICIs to illicit dramatic and durable responses, well-validated biomarkers that can be effectively implemented in the clinic will require strong negative predictive values that do not limit patients with who may benefit from ICI therapy.

Keywords: Biomarker; CTLA-4; Checkpoint inhibitor; Melanoma; PD-1.

Figure 1. The process of T cell mediated anti-tumor immunity and associated biomarkers

The process of T cell mediated anti-tumor immunity is outlined. Sources of potential molecular or biological biomarkers along this process are identified.

Figure 2. The spectrum of biomarkers for response and/or resistance to immune checkpoint inhibition

Biological or clinical sources of reported biomarkers are designated and color coded according to positive association with response (green), positive association with resistance (red), or mixed interpretation (blue).