Skin Immune Responses and Oncogenesis: A Delicate Balance

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.

This review synthesizes current findings on the dual role of skin immunity in cancer, focusing on mechanisms of immune surveillance, evasion, and therapeutic restoration.

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.

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.