A decade of checkpoint blockade immunotherapy in melanoma: understanding the molecular basis for immune sensitivity and resistance

Enormous progress has been made in the ten years since immune checkpoint blockade (ICB) was first approved for treating melanoma. Zappasodi and Huang review the current state of the art of ICB for melanoma and prospects for the future. Ten years since the immune checkpoint inhibitor ipilimumab was approved for advanced melanoma, it is time to reflect on the lessons learned regarding modulation of the immune system to treat cancer and on novel approaches to further extend the efficacy of current and emerging immunotherapies. Here, we review the studies that led to our current understanding of the melanoma immune microenvironment in humans and the mechanistic work supporting these observations. We discuss how this information is guiding more precise analyses of the mechanisms of action of immune checkpoint blockade and novel immunotherapeutic approaches. Lastly, we review emerging evidence supporting the negative impact of melanoma metabolic adaptation on anti-tumor immunity and discuss how to counteract such mechanisms for more successful use of immunotherapy.

Automated summary

Enormous progress has been made in the treatment of melanoma using immune checkpoint blockade in the past ten years. This review discusses the current understanding of the melanoma immune microenvironment and explores novel approaches to enhance the efficacy of immunotherapies. It also highlights the negative impact of melanoma metabolic adaptation on anti-tumor immunity and proposes ways to counteract these mechanisms for more effective use of immunotherapy.