3044 - Carbon Ion Therapy-Induced Local Control of Pancreatic Cancer is Dependent on the Presence of the Adaptive Anti-Tumor Immunity
Presenter(s)
S. Eskandarian1,2, M. Moustafa1,2, M. Akbarpour1,2, B. I. Bell3,4, H. J. Meyer2,5, S. Brons6, A. Gahlawat1,2, J. Schlegel1,2, I. Dokic1,2, M. Knoll1,2, C. Guha3,4, and A. Abdollahi1,2; 1Clinical Cooperation Unit Translational Radiation Oncology, National Center for Tumor Diseases (NCT), Heidelberg University Hospital (UKHD) and German Cancer Research Center (DKFZ), Heidelberg, Germany, 2Division of Molecular and Translational Radiation Oncology, Department of Radiation Oncology, Heidelberg Faculty of Medicine (MFHD), Heidelberg University Hospital (UKHD) and Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg, Germany, 3Department of Radiation Oncology, Montefiore Medical Center, Bronx, NY, 4Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, 5Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, 6Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation Oncology, Heidelberg University Hospital (UKHD), Heidelberg, Germany
Purpose/Objective(s): Carbon ion radiotherapy (CIRT) has shown promising clinical outcomes in pancreatic ductal adenocarcinoma (PDAC). We sought to investigate the impact of adaptive immune response on CIRT induced tumor control probability (TCP).
Materials/Methods: KPCY-2838c3 tumor derived from LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre; YFP, KPCY genetically engineered mouse model (GEMM) were subcutaneously implanted into syngeneic immunocompetent C57BL/6. Mice were randomized when tumors reached 80 ± 30 mm3. Tumors were irradiated at the mid region of the spread-out Bragg peak (SOBP, LETd of 95 keV/µm). Dose escalation series was conducted at five consecutive daily fractions of 3, 4, 5, and 6 Gy. To evaluate the impact of the adaptive T-cell response, all experiments were also conducted in immunocompromised nude mice. The impact of cytotoxic T-Cell response was further functionally validated using anti-CD8 (aCD8) depleting antibodies.
Results: The TCP gradually increased from 50% at 5x3Gy to 100% after 5x6Gy. In contrast, TCP was not reached up to 5x6Gy in nude mice lacking anti-tumoral T-cell immunity. Moreover, depletion of cytotoxic T-cells by aCD8 reduced CIRT induced TCP efficacy.
Conclusion: High-LET CIRT efficiently eradicates otherwise therapy resistant KPC GEMM. Adaptive anti-tumoral T-cell response plays a pivotal role for achievement of tumor control governed by CIRT in PDAC.