EGFR-targeted photoimmunotherapy and its association with the immune microenvironment in locoregional recurrent head and neck squamous cell carcinoma

Background Epidermal growth factor receptor (EGFR)-targeted photoimmunotherapy using cetuximab sarotalocan sodium (RM-1929) represents a novel therapeutic modality that induces selective tumor cell death and may influence the tumor immune microenvironment (TIME) in head and neck squamous cell carcinoma (HNSCC). However, its immunological consequences are not well defined. Methods We retrospectively evaluated 25 patients with locoregional recurrent HNSCC who received RM-1929 photoimmunotherapy to evaluate treatment response, overall survival (OS), and safety. To explore TIME features, 14-marker multiplex immunohistochemistry was performed on pretreatment tumor samples from 14 patients, with 6 paired pre- and post-treatment samples. Results Across 40 treatment cycles, the overall response rate was 77.5% (7 complete, 24 partial responses) with a median OS of 401 days. Treatment was generally well tolerated, with adverse events limited to expected local toxicities. Clinical responses were not explained by conventional clinicopathological factors or EGFR expression on tumor cells. In TIME analysis, responders exhibit significantly higher intratumoral CD39 + CD8 + T cell density compared with non-responders. Longitudinal analyses revealed qualitative remodeling of the TIME after therapy, redistribution of CD8 + T cells and increasement of PD-L1 + immune cells. Conclusion RM-1929 photoimmunotherapy demonstrated local efficacy with limited adverse events. Distinct TIME characteristics and potential immune remodeling, involving CD39 + CD8 + T cell, were observed. These observations provide a rationale for further investigation of photoimmunotherapy as a strategy to integrate local tumor ablation with systemic immune modulation in recurrent HNSCC.