Skin Immune Responses and Oncogenesis: A Delicate Balance

Abstract

Background: The skin contains a complex immune network involving keratinocytes, Langerhans cells, tissue-resident memory T cells, regulatory T cells, and B cells that collectively maintain immune surveillance and homeostasis. Methods: This review synthesizes current findings on the dual role of skin immunity in cancer, focusing on mechanisms of immune surveillance, evasion, and therapeutic restoration. Results: Keratinocytes detect pathogens through pattern-recognition receptors and secrete cytokines such as IL-1, IL-6, IL-10, and TGF-β to balance inflammation. Langerhans cells capture antigens and activate T lymphocytes, while NK cells and cytotoxic T cells eliminate transformed cells. However, ultraviolet radiation and oncogenic viruses (e.g., β-HPVs) induce DNA mutations and immunosuppressive mediators that impair local immunity. Tumor cells further evade immune attack by upregulating checkpoint ligands (PD-L1, CTLA-4), secreting TGF-β and IL-10, and reprogramming metabolism to promote a hypoxic, tumor-supportive microenvironment. Conclusion: Understanding how immune surveillance shifts toward immune escape remains a major challenge. Therapies targeting these mechanisms, checkpoint inhibitors, adoptive cell therapy, oncolytic viruses, microbiome modulation, and nanotechnology-based delivery, represent promising strategies to restore effective antitumor immunity in the skin.