Abstract 65: Real time imaging of the non-small cell lung cancer immune microenvironment modulation by low dose photodynamic therapy

Abstract Immune checkpoint inhibitors (ICIs) have significantly improved the outcome of non-small cell lung cancers (NSCLCs). However, cancer response to ICIs occurs in a fraction of patients and correlates with the presence of tumor-infiltrating lymphocytes (TILs). Thus, methods to increase the presence of TILs within lung cancer are urgently needed. Previously, in a murine model of malignant pleural mesothelioma, we described a mechanism by which low dose photodynamic therapy (L-PDT) enhanced the vascular expression of E-selectin which favored TILs recruitment and improved tumor control. Here, we hypothesized that a similar mechanism existed in NSCLC and could be further potentiated by ICIs.We developed a murine model with a chest window allowing real time imaging by two-photon microscopy of lung adenocarcinoma (LUAD, 344-SQ-GFP, KrasG12D; p53R172HΔG mutant) growing in the lungs of C57BL/6-CD2-dsRed transgenic mice. We determined the impact of L-PDT±E-selectin blocking antibodies (EBA) on CD2+TILs recruitment over 30 days. In a separate experiment, we then assessed the impact of L-PDT±EBA on tumor growth, animal survival and spontaneous metastasis development. Finally, we characterized the LUAD immune microenvironment and TILs immune checkpoint expression 1 and 5 days after L-PDT by 16-colors flow cytometry. L-PDT significantly enhanced the recruitment of CD2+TILs, with a significant increase observed at day 1, that lasted up to 20 days post-treatment compared to controls. L-PDT was significantly correlated with improved tumor control (-42%), a significant reduction in metastasis development (-50%) and an increase in animal survival (+26%) compared to the control group. Interestingly, this phenotype was abrogated to control levels when L-PDT was combined with EAB. Further analysis of the tumor immune microenvironment confirmed the recruitment of CD8+ T lymphocytes at both 1- and 5-days following L-PDT with increased PD-1 expression on their surface day 5 post-treatment compared to controls. L-PDT triggers, through vascular E-Selectin, a durable infiltration of NSCLCs by TILs which provide better tumor control, impair metastasis development, and improve animal survival. The increased PD-1 levels on CD8-T cells following L-PDT suggest a favorable combination with PD1/PDL1 inhibitors. Citation Format: Damien N. Marie, Louis-Emmanuel Chriqui, Alexandros Sifis, Etienne Abdelnour, Michel Gonzalez, Thorsten Krueger, Johanna A. Joyce, Sabrina Cavin, Jean Y. Perentes. Real time imaging of the non-small cell lung cancer immune microenvironment modulation by low dose photodynamic therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 65.