Purpose: Local tumor growth is a major cause of morbidity and mortality in nearly 30% of patients with pancreatic ductal adenocarcinoma (PDAC). Radiotherapy (RT) is commonly used for local disease control in PDAC, but efficacy is limited. We studied the impact of selectively intervening on RT-induced inflammation as an approach to overcome resistance to RT in PDAC. Experimental Design: PDAC cell lines derived from primary pancreatic tumors arising spontaneously in KrasLSL-G12D/+;Trp53LSL-R172H/+;Pdx-1 Cre (KPC) mice were implanted into syngeneic mice and tumors were focally irradiated using the Small Animal Radiation Research Platform (SARRP). We determined the impact of depleting T cells and Ly6C+ monocytes as well as inhibiting the chemokine CCL2 on RT efficacy. Tumors were analyzed by flow cytometry and immunohistochemistry to detect changes in leukocyte infiltration, tumor viability and vascularity. Assays were performed on tumor tissues to detect cytokines and gene expression. Results: Ablative RT alone had minimal impact on PDAC growth but led to a significant increase in CCL2 production by tumor cells and recruitment of Ly6C+CCR2+ monocytes. A neutralizing anti-CCL2 antibody selectively inhibited RT-dependent recruitment of monocytes/macrophages and delayed tumor growth but only in combination with RT (p<0.001). This anti-tumor effect was associated with decreased tumor proliferation and vascularity. Genetic deletion of CCL2 in PDAC cells also improved RT efficacy. Conclusions: PDAC responds to RT by producing CCL2, which recruits Ly6C+CCR2+ monocytes to support tumor proliferation and neovascularization after RT. Disrupting the CCL2-CCR2 axis in combination with RT holds promise for improving RT efficacy in PDAC. Anusha Kalbasi, Chad A. Komar, Graham M. Tooker, Mingen Liu, Jae W Lee, Whitney L. Gladney, Edgar Ben-Josef and Gregory L. Beatty Download Paper
Xstrahl to Highlight Superficial and Orthovoltage Radiotherapy Solutions for Skin Cancer and Selective Benign Conditions at ACRO Summit 2025 in Las Vegas
Xstrahl, a global leader in the delivery of superficial radiation therapy devices and preclinical radiation research systems, will demonstrate Xstrahl 200, a modern orthovoltage radiotherapy solution for treating superficial lesions, skin cancers, and selective benign conditions. Visit Xstrahl at booth 220 at the ACRO Summit 2025 – The Radiation Oncology Summit located at Planet Hollywood, Las Vegas, NV from March 12-15, 2025.