Immunotherapy for Rare and Hard-to-Treat Skin Cancers: Molecular Mechanisms, Clinical Strategies, and Toxicity Management

Rare and hard-to-treat skin cancers, such as Merkel cell carcinoma, advanced cutaneous squamous cell carcinoma, refractory basal cell carcinoma, atypical fibroxanthoma, pleomorphic dermal sarcoma, adnexal carcinomas, and related cutaneous sarcomas, pose major therapeutic challenges. Many patients are older and comorbid, diagnoses are often delayed, and standard surgery, radiotherapy, or systemic therapies may be insufficient or not feasible. Immune checkpoint inhibitors and other immunotherapies have begun to change outcomes in several of these entities, yet responses remain variable, resistance is common, and immune-related toxicities can be difficult to manage in this population.This Research Topic aims to bring together mechanistic, translational, and clinical studies to optimize the use of immunotherapy in rare and hard-to-treat skin cancers. We seek contributions that clarify how tumour mutational burden, UV-associated mutational signatures, the immune microenvironment, and related biomarkers shape response and resistance to immune checkpoint inhibitors and other immunotherapies, and how these insights can guide patient selection, treatment sequencing, and duration. At the same time, we aim to capture real-world outcomes, neoadjuvant and adjuvant strategies, rational combinations with surgery and radiotherapy, and practical approaches to diagnosing, preventing, and managing immune-related toxicities in these often vulnerable patient populations, ultimately supporting more precise and effective care.We invite submissions on immunotherapy for rare and hard-to-treat skin cancers, including but not limited to Merkel cell carcinoma, advanced cutaneous squamous cell carcinoma, refractory basal cell carcinoma, atypical fibroxanthoma, pleomorphic dermal sarcoma, adnexal carcinomas, and other cutaneous sarcomas. Contributions may address preclinical, translational, or clinical aspects, for example:• Molecular and immunological mechanisms of response and resistance to immune checkpoint inhibitors and other immunotherapies.• Characterization of the tumour immune microenvironment, tumour mutational burden, and other potential predictive or prognostic biomarkers.• Clinical strategies and outcomes in neoadjuvant, adjuvant, or metastatic settings, including combinations and sequencing with surgery or radiotherapy.• Real-world evidence, case series, and cohorts in rare or ultra-rare skin cancers treated with immunotherapy.• Patterns, risk factors, and management of immune-related adverse events in this patient population.We welcome Original Research, Reviews, Mini-Reviews, Case Reports, Clinical Trial articles, and Perspectives or Opinions. We encourage multidisciplinary contributions that help refine and personalize immunotherapy for patients with rare and hard-to-treat skin cancers.Please note: manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal. Topic editors: BIANCA ARIANNA FACCHINI, Francesca Sparano, Victor Desmond Mandel Source: https://www.frontiersin.org/research-topics/79161/immunotherapy-for-rare-and-hard-to-treat-skin-cancers-molecular-mechanisms-clinical-strategies-and-toxicity-management