Abstract 1289: Systemic immune response of prostate cancer patients to alpha-emitting radiotherapy

Abstract

Abstract Targeted alpha therapy (TAT) is a type of radiotherapy (RT) that uses alpha-emitting radionuclides. These radionuclides have a natural affinity for areas of bone metastases (i.e., radium-223, Ra-223) or can label specific tumour targets (i.e., prostate-specific membrane antigen). Conventional photon irradiation (i.e., external beam) can activate or suppress immune responses. The resulting immune response is dictated by the release of soluble markers such as cytokines (i.e., IL-6) and damage associated molecular patterns, DAMPs (calreticulin). Less is known about the immune response induced by alpha-emitters. With increased interest in using TAT for cancer patients, it is important to gain a more in depth knowledge regarding the immune response of alpha emitters. Aim: Explore the systemic immune response of prostate cancer (PCa) patients to alpha-emitting RT by studying circulating cytokines, checkpoint molecules, matrix metalloproteinases (MMPs) and DAMPs. Methods: The cohort comprised of 43 patients with metastatic castration-resistant PCa treated with up to six four-weekly injections of the alpha emitter, Ra-223. We measured longitudinal changes in 61 plasma markers using the Luminex assay. The plasma markers included cytokines, checkpoint molecules and DAMPs. Results: Ra-223 induced longitudinal changes in 14 plasma markers over the course of treatment (T2-T6) compared with pre-treatment levels (T1). Most of the observed RT-induced changes occurred after four injections of Ra-223 (T5), where 9 of the 14 plasma markers changed significantly. The table summarises T5 findings (presented as mean concentration, pg/ml; statistical analysis using Wilcoxon matched-pairs signed rank test). Conclusion: Our data demonstrates that alpha-emitting RT induces systemic immune responses that can be measured in the plasma of patients. Given the diverse role of these markers, further study is needed to explore the biological implications of these systemic changes on patient outcome. Changes in plasma markers in patients treated with Ra-223 T1 T5 P value IL-8 6.7±0.9 9.7±1.3 0.0009 IL-2R 293.5±42.9 364.5±69.7 0.0247 IP-10 18.4±2.3 21.8±2.5 0.0243 RANTES 2668.8±173.4 2944.7±164.6 0.0455 BTLA 549.9±153.5 527.7±265.2 0.0319 CD137 49.6±8.9 39.1±13.5 0.0099 Calreticulin 7868±3514.9 9238.4±808.5 0.0386 RAGE 63.9±4.7 52.3±5.1 0.0014 MMP1 66.1±7.5 84.9±12.6 0.0245 Citation Format: Sapna Lunj, Hitesh Mistry, YeePei Song, Kamlesh Patel, Hannah Nightingale, Tim Smith, Peter Hoskin, Catharine West, Ananya Choudhury. Systemic immune response of prostate cancer patients to alpha-emitting radiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1289.