Improvement of Melanoma Immune Checkpoint Blockade Therapy with Potential Combinatorial Regiments

With the increasing incidence rate of melanoma globally, it becomes urgent to develop novel therapeutic regimens in addition to traditional treatments, namely surgery, chemotherapy, radiotherapy, etc. Immune checkpoint blockade (ICB) is regarded as a revolutionary breakthrough. Blockades of PD-1, PD-L1, and CTLA-4 have become promising first-line treatments for patients with advanced or metastatic cutaneous melanoma in the last decade. However, the clinical response rates are still unsatisfactory, and the durable clinical benefit remains limited. The potential mechanisms have been intensively investigated and well documented, such as lack of tumor specific neoantigen, immune suppressive microenvironment, T cell exhaustion, etc. Accordingly, multiple regimens have been proposed to combine with ICB therapy, and some of them have been put to clinical practice, e.g., cytolytic chemotherapy with PD-1/PD-L1 agents, radiotherapy with PD-1/PD-L1 agents, angiogenesis inhibitor (such as Avastin) with PD-1 agents, compensatory immune checkpoint blockade (combination of PD-1 and CTLA-4 blockers, or that of PD-1 and PD-L1 blockers), microenvironment immune modulator (such as IDO/TDO inhibitors) with PD-1 agents, and T cell activator (cytokines, such as IL-2 and IL12) with PD-1/PD-L1 agents. All these combinatorial regimens potentially enhance the efficacy of ICB drugs, which makes them one of the most popular topics in cancer research field.

The aim of this Research Topic is 1) to present the most rational and pioneering combined strategies to improve the therapeutic effects of Immune checkpoint inhibitors in treating melanoma (especially for those in advanced stage) with minimal toxicity, 2) to extend the understanding of the mechanisms by which these approaches synergize to enhance anti-tumor immunity, 3) to develop novel drug delivery systems which coordinate the combination regimens and diminish side effect of ICB, and 4) to identify and validate biomarkers for predicting efficacy and/or toxicity.

We welcome submissions of Original Research, Review, Mini Review and Case Report on the following aspects of the combined immunotherapy for melanoma:
• Novel and effective combinatorial regimens that synergize therapeutic effect of current ICB drugs (such as PD-1, PD-L1, and CTLA-4 agents)
• Mechanisms of combined therapy to enhance the curative effect of ICB therapy
• Identification and validation of biomarkers for ICB drug response and toxicities, and targets to improve ICB therapy
• Development of novel drug delivery system for ICB therapy