Navigating a Complex Intersection: Immunotherapy and Radiotherapy Synergy in Squamous Cell Carcinoma of the Skin—A Comprehensive Literature Review

Skin squamous cell carcinoma (SCC) represents a major public health concern due to its high incidence and potential for local invasion and metastasis. Compared to local recurrence, metastatic SCC represents an even greater therapeutic challenge. Once distant metastasis occurs, the disease becomes incurable, and treatment focuses on palliation and prolonging survival. The immune microenvironment of SCC is characterized by an infiltration of immune cells, including tumor-infiltrating lymphocytes. In addition to its direct cytotoxic effects, radiotherapy also induces immunomodulatory effects within the tumor microenvironment. Radiation can promote the release of tumor-associated antigens and induce immunogenic cell death, thereby enhancing the recognition of tumor cells by the immune system. Immunotherapy and radiotherapy have emerged as promising therapeutic modalities for metastatic SCC. This literature review aims to evaluate the potential synergy between these treatments and shed light on their combined efficacy. Within the manuscript, we present a compelling case report of a patient with advanced SCC who exhibited resistance to the combined regimen of immunotherapy and radiotherapy, leading to disease progression. Despite the increasing evidence supporting the synergy between these modalities, this case underscores the complex nature of treatment response and the importance of considering individual patient characteristics.