Intratumoral Immunotherapy—The Future of Treating Merkel Cell Carcinoma?

Merkel cell carcinoma (MCC) represents a rare but highly aggressive neuroendocrine skin cancer with limited systemic therapy options for patients who fail or are ineligible for immune checkpoint inhibitors (ICIs). Intratumoral (IT) immunotherapy has emerged as a promising strategy, leveraging the accessibility of tumor lesions and their inherent capacity to trigger immune responses, known as abscopal effects. This review synthesizes the current evidence on IT approaches in MCC, including Toll-like receptor agonists, cytokines, and oncolytic viruses, and highlights their distinct mechanisms of action, while emphasizing the critical need for standardized radiographic response assessment of injected and non-injected lesions. Inconsistent documentation of abscopal responses has hindered quantification of IT therapy’s systemic potential, particularly in a disease where one-third of patients present with metastases and distant relapse is common. We outline MCC-specific rationale for routine lesion-level tracking, and recommendations for IT trial designs and objectives. Rigorous assessments of abscopal data will clarify IT’s role as both rescue therapy and an ICI partner, potentially transforming outcomes in this refractory MCC.