Abstract 4532: Investigating the effects of radiation and anti-PD1 therapy on immune cell tumor infiltration in head and neck cancer

Abstract Head and neck cancer (HNC) is predominantly comprised of head and neck squamous cell carcinoma (HNSCC), ranking as the 6th most common cancer worldwide. There are roughly 450,000 documented annual fatalities with predictions of annual increases in incidence. Despite advances in these intensive anticancer techniques, patient survival remains low. The current standard of care for local recurrence of HNSCC tumors is salvage surgery (SS) or combined modality with adjuvant re-irradiation using (X-ray)-based therapy (XRT). However, due to critical structure dose limits of the head and neck region, adjuvant XRT can cause excess morbidity. Proton radiation (PT), although less researched, may be advantageous to minimize the risk of injury to highly critical structures and minimize the radiation dosage outside of the tumor volume due to its energy course of the Bragg’s Peak, which is thought to also have a higher relative biological effectiveness. While there may be high clinical relevancy of PT, there is currently a lack of translational and clinical data to confirm advantages of its use in HNSCC. Patients with HNSCC have impaired immune surveillance, and higher levels of inhibitory checkpoints such as PD-L1 permitting tumors to evade the immune system. Immunotherapy targeting PD-1, receptor to PD-L1, has greatly enhanced survival rates in these patients, but many patients fail to respond due to other immunosuppressive factors. Here we investigate the immune response effects of RT, with either XRT or PT combined with anti-PD1 antibody (αPD1) in vivo using an established murine oral cavity tumor model. Wild-type C57BL/6 mice were injected into the buccal region with 1.5 x 106 mouse oral cavity (MOC-1) cells. Once tumors reached 50-150mm3, mice were treated over one week with XRT (3 treatments of 5 Gy) or sham. The following week the mice received αPD1 or IgG isotype control antibody. Here we present effects of XRT vs PT on immune infiltration by flow cytometry and immunofluorescence in three independent studies. Growth curves in the studies indicated that proton therapy and αPD1 in combination may be advantageous over αPD1 or PT alone with increased CD8 T cell infiltration, suggesting that PT in combination with αPD1 may offer significant advantages in eliciting a strong anti-tumor immune response. Citation Format: Katelyn Jansen, Maria Lehn, Nicolas Nassar, Alexis Redmond, Mathieu Sertorio, Vinita Takiar, Dalia El-Gamal, Trisha Wise-Draper. Investigating the effects of radiation and anti-PD1 therapy on immune cell tumor infiltration in head and neck 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 4532.