From Spontaneous Melanoma Regression to Checkpoint-Induced Skin Autoimmunity: Shared Immune Mechanisms at the Intersection of Anti-Tumor and Autoimmune Responses

The dual relationship between autoimmunity and anti-tumor immunity represents a critical and increasingly recognized frontier in modern immunology, with the skin serving as both the most frequent and the most accessible site where these processes converge. While effective anti-tumor immune responses can drive tumor regression, they are regularly accompanied by cutaneous autoimmune manifestations — either arising spontaneously in the context of neoplasia or induced by immunotherapy.This Research Topic aims to dissect the shared cellular and molecular mechanisms underlying these phenomena, with a particular focus on how immune activation can simultaneously mediate tumor control and tissue-specific, especially cutaneous, autoimmunity. Recent advances in immune checkpoint inhibitors and other immunotherapies have highlighted the clinical relevance of cutaneous immune-related adverse events (cirAEs), which affect more than 50% of treated patients and may serve as both therapeutic challenges and potential biomarkers of treatment efficacy.By integrating clinical observations with mechanistic insights, this collection seeks to advance our understanding of how to optimize anti-cancer immunity while minimizing collateral cutaneous autoimmune toxicity. Emerging evidence suggests that anti-tumor immune responses and autoimmune processes are closely intertwined, often sharing common antigenic targets and immune effector pathways — and the skin represents the paradigmatic organ in which this overlap becomes clinically visible.Spontaneous phenomena such as melanoma regression, halo nevus formation, vitiligo-like depigmentation, and lichenoid reactions at sites of actinic keratoses illustrate how immune recognition of tumor-associated melanocytic or keratinocytic antigens can extend to normal skin tissues. Similarly, immune checkpoint blockade therapies have demonstrated unprecedented clinical success, but frequently induce a broad spectrum of cutaneous irAEs, reflecting a breakdown in immune tolerance at the skin level.This spectrum ranges from self-limiting inflammatory dermatoses — including maculopapular exanthemas, psoriasiform, lichenoid, and eczematous reactions — to classic autoimmune skin diseases such as vitiligo, dermatomyositis, cutaneous lupus erythematosus, and autoimmune blistering disorders including bullous pemphigoid and paraneoplastic pemphigus, to rare but potentially life-threatening conditions such as Stevens-Johnson syndrome and toxic epidermal necrolysis.Importantly, several of these cutaneous manifestations have been associated with favorable oncological outcomes, suggesting that they may serve not only as clinical challenges but as immunological biomarkers of effective anti-tumor response. These observations underscore the need to better understand the immunopathological mechanisms underlying cutaneous irAEs and to bridge dermatology, oncology, and translational immunology to unravel these complex interactions.This Research Topic welcomes contributions that explore the intersection of autoimmunity and anti-tumor immunity, with a particular emphasis on cutaneous and dermatological manifestations, from both mechanistic and clinical perspectives.Topics of interest include, but are not limited to:- Shared tumor-associated and cutaneous autoantigens (melanocytic, keratinocytic, basement membrane zone) driving both anti-tumor and autoimmune responses- Immune tolerance and its breakdown in the skin under checkpoint inhibitor therapy- Pathogenesis and immunopathology of specific cutaneous irAE entities, including lichenoid reactions, psoriasiform dermatitis, vitiligo, cutaneous lupus erythematosus, dermatomyositis, bullous pemphigoid, pemphigus, and severe cutaneous adverse reactions (SJS/TEN)- Spontaneous anti-tumor autoimmunity in the skin: melanoma regression, halo nevi, lichenoid actinic keratoses, and paraneoplastic dermatoses- Cutaneous biomarkers of immune activation, irAE risk stratification, and ICI treatment response- Histopathological and molecular characterization of cutaneous irAEs versus idiopathic autoimmune dermatoses- Keratinocyte biology, skin barrier function, and the cutaneous microenvironment in irAE pathogenesis- Therapeutic strategies to manage cutaneous irAEs while preserving anti-tumor efficacy, including targeted biologics (dupilumab, omalizumab, anti-IL-17, anti-IL-23) and JAK inhibitors- Multidisciplinary oncodermatological approaches integrating dermatology, oncology, and translational immunology- Submissions may include original research articles, reviews, mini-reviews, clinical studies, case series with mechanistic insights, and perspective pieces. Contributions that integrate translational insights with clinical relevance, particularly those bridging dermatoimmunology and oncology, are especially encouraged.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: Joerg Wenzel, Dennis Niebel, Luka de Vos Source: https://www.frontiersin.org/research-topics/81284/from-spontaneous-melanoma-regression-to-checkpoint-induced-skin-autoimmunity-shared-immune-mechanisms-at-the-intersection-of-anti-tumor-and-autoimmune-responses