Abstract 1340: Interstitial photodynamic therapy enhances the efficacy of immune checkpoint inhibitor in estrogen receptor high-expressing breast cancer

Introduction: Systemic chemotherapies improve the response to immune checkpoint inhibitors (ICIs) by provoking an immune response in primary breast cancer (BC). However, chemotherapy has systemic side effects, and recent clinical trials in estrogen receptor (ER)-positive BC have shown that higher expression of ER correlates negatively with response to ICI, even when combined with systemic chemotherapy. Photodynamic therapy (PDT) that uses light to activate a photosensitive drug not only ablates primary tumors but also enhances systemic immune response with minimal systemic adverse effects. We hypothesized that ER high-expressing BC will respond to ICI when combined with interstitial PDT (I-PDT), which allows deep light penetration with minimum skin damage by illuminating the tumor with optical fibers inserted directly into the tumor. Methods: Two syngeneic murine BC cells tagged with luciferase (TS/A-luc: BALB/c background with high ER expression, and E0771: C57BL/6 background with low ER expression) were surgically inoculated into #2 mammary fat pad of 6-8 weeks old female mice. I-PDT (Verteporfin, 2 mg/kg and 689-nm laser light) with/without anti-PD-1 i.p. (200 µg/mouse) was performed when tumors reached 8mm. “Cure” was defined as the absence of detectable tumors by caliper measurement and bioluminescence 60 days after I-PDT. Results: Response to I-PDT alone was compared between TS/A-luc and E0771-luc models with differing levels of ER expression. I-PDT treatment delayed the growth in all TS/A-luc tumors (6/6), whereas only half of E0771-luc tumors (3/6) were delayed. Among the mice that initially responded to I-PDT, 5 out of 6 mice with TS/A-luc and all 3 mice with E0771-luc demonstrated local recurrence, and the cure rates were 16.7% (1/6) for TS/A-luc and 0% (0/6) for E0771-luc models treated with I-PDT alone. Next, ICI treatment alone did not show any change in ER high-expressing TS/A-luc tumor growth, which is similar to what we see in human patients. On the other hand, the combination of I-PDT and anti-PD-1 demonstrated the cure rate of 43.8% (7/16) in TS/A-luc tumors. Conclusion: Our study showed that I-PDT delayed the tumor growth in both TS/A-luc and E0771-luc syngeneic murine models. Further, I-PDT enhanced the efficacy of ICIs in TS/A-luc model, which expresses high ER. These findings show the potential of I-PDT as a combinatorial approach with ICIs in ER-positive BC. Citation Format: Kohei Chida, Emily Oakley-Gawrys, Christopher Lawson, Amber McKenery, Craig M. Brackett, John M. Ebos, Kenichi Hakamada, Gal Shafirstein, Kazuaki Takabe. Interstitial photodynamic therapy enhances the efficacy of immune checkpoint inhibitor in estrogen receptor high-expressing breast cancer [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 1340.