Histopathological analysis of tumor microenvironmental changes after near-infrared photoimmunotherapy

Objective: Although NIR-PIT has been approved in Japan for recurrent and previously treated head and neck cancer, detailed analysis of tumor microenvironment remains lacking. This study aimed to evaluate the effects of near-infrared photoimmunotherapy (NIR-PIT) on the tumor microenvironment, focusing on tumor blood vessels delivering antibodies and immune cells to tumor tissue and macrophages migrating through tumor blood vessels into tumor tissue after NIR-PIT, in a mouse model of human tongue carcinoma. Methods: A mouse tumor model using SAS human tongue carcinoma cell lines was utilized to investigate changes in necrosis, blood vessels, and macrophage infiltration 24 hours after NIR-PIT. The NIR-PIT treatment involved the photoactivation of IRDye®700DX (IR700)-conjugated antibodies with near-infrared light. Histological analysis assessed necrotic tissue, the number and distribution of open vessels, and macrophage recruitment. Results: At 24 hours post-NIR-PIT, necrotic tumor areas were three times larger, while the number of open blood vessels and macrophage recruitment increased by two to three times compared to controls. These findings suggest that NIR-PIT enhances the tumor immune response by expanding the tumor vascular lumen and facilitating macrophage infiltration. Conclusions: NIR-PIT promotes vascular changes and enhances macrophage recruitment, which could improve drug delivery and enhance the antitumor immune response. The combination of NIR-PIT with chemotherapy may further increase therapeutic efficacy. While the lack of cellular immunity in nude mice limited conclusions on immune activation, this study provides the first histological evidence of innate immune involvement in short-term tissue changes after NIR-PIT, supporting its potential as an effective cancer treatment.