Current Insights in Melanoma Immunology, Immune Escape and Immunotherapy Advances

Melanoma is an immunologically “warm” tumour characterized by the expression of multiple tumour-associated antigens by malignant cells, which can be targeted by the host immune system. Additionally, spontaneous immune responses against these tumour-associated antigens are frequently observed in melanoma patients. Immune responses against melanoma (e.g., their magnitude as well as their duration) are mainly regulated by the immune system itself, but melanoma cells can resort to overt evasive activities (e.g., downregulation of targetable molecules, overexpression of immunosuppressive cytokines, exhaustion of activated T lymphocytes). More than 10 years since the approval of ipilimumab, it is time to reflect on the lessons learned regarding immune modulation to treat cancer on a more individualized basis and on novel approaches (from immune checkpoint inhibitors, bispecific antibodies, and individualized neoantigen vaccines to adoptive cell therapy) to further extend the efficacy of current and emerging immunotherapies. Unleashing the adaptive immunity with immune checkpoint inhibitors (ICIs) has drastically improved the clinical outcomes of patients with advanced or metastatic melanoma. Still, a high proportion of treated patients derive no benefit from immunotherapy due to primary or acquired resistance to ICIs. Therefore, advancing melanoma patient care necessitates a deeper understanding of the immune dynamic interplay between melanoma cells, tumour immune microenvironment constituents, and immunotherapeutic agents.

The objective of this Research Topic is to shape a comprehensive collection of research and review articles that delve into the intricate mechanisms behind melanoma immunology and immunotherapy rationale. Our primary focus lies on elucidating the pleiotropic effects of the ever-growing arsenal of immunotherapeutic agents, identifying and describing critical immunologic pathways and mechanisms that are implicated in the anti-melanoma immune response. We further welcome preclinical and clinical data that i) will focus on molecular and cellular biomarkers for personalized immunotherapeutic decisions and ii) will help with the management of immune-related adverse events.

We welcome the submission of Original Research articles, Systematic Reviews, Narrative Reviews, Mini Reviews, Case Reports and Case Studies, Clinical Trials and Study Protocols. Authors are encouraged to address a range of topics, including, but not limited to:
• Tumor immune microenvironment dynamics: Investigation of the impact of tumor immune microenvironment on the antimelanoma immune response and identification of factors that contribute to immune evasion.
• Clinical effects of immunotherapy administration on different immune cell subsets in melanoma patients
• Insights into the intratumoral and systemic mechanisms of melanoma resistance to immunotherapy
• Cellular or molecular biomarkers: Identification and validation of biomarkers that can predict immunotherapy response and guide tailored approaches.
• Novel pathophysiological, genetic, and epigenetic models to evaluate melanoma evolution and treatment
• New strategies for boosting immune response in early and advanced melanoma disease
• Preclinical and clinical evidence on combination of immunotherapeutic approaches
• New checkpoint molecules and other targetable immunologic candidates
• The synergistic (or not) role of targeting various molecules/pathways
• Clinical data on the diagnosis and management of immune-related adverse events.


Please note that Dr. Pedro Berraondo reports research funding from Moderna, Affimed, Hookipa, and Bavarian Nordic and speaker honoraria from BMS, MSD, Novartis, and AstraZeneca.

Please also note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.