Abstract 677: Immune biomarkers of response to Ra223 dichloride and stereotactic body radiation therapy in patients with oligometastatic prostate cancers

Abstract

Abstract Prostate cancer is the second leading cause of death in men in the developed countries. Androgen deprivation therapy (ADT) is commonly used to treat prostate tumors at earlier stages due to hormone-dependence of cancer cells. However, the onset of androgen-resistance with tumor progression and the negative impact of ADT on the quality of life are significant challenges. To address these issues, we have initiated a novel clinical trial combining radium Ra223 dichloride with stereotactic body radiation treatment (SBRT) and short course of ADT in patients with oligometastatic, castration-sensitive prostate cancer (NCT03351735). Patients with one to four oligometastatic prostate cancer lesions have been receiving ADT for nine months, together with SBRT to all metastatic sites and six cycles of Ra223 to target micrometastatic bone lesions. Eight out of the planned 24 patients have already completed the full treatment course, with five patients currently on surveillance (not requiring any further treatment) and three patients receiving next cycle of therapy. As part of this investigator-initiated study, we have performed a comprehensive immune characterization of peripheral immune cells and serum immune biomarkers in all treated patients. Based on flow cytometric analysis, we found a significant decrease in the percentage of CD4+ T cells befoe and after SBRT (cycle 1) but no changes in the elevated levels of programmed cell death-1 (PD-1), a marker of T-cell exhaustion, on the circulating CD4+ and CD8+ T cells. In addition, we observed high levels of the activated STAT3 (pSTAT3) in myeloid-derived suppressor cells (MDSCs), together with its downstream target Arginase-I. Finally, IL-8 stood out as a cytokine strongly elevated in plasma of patients who received the complete Ra223 treatment but not directly after SBRT. Overall, these preliminary results suggest that this combinatorial radiotherapy patients with oligometastatic prostate cancers impacts immune cell activity but rather than leading to T cell activation it may promote tolerogenic activity of MDSCs. Citation Format: Marice Alcantara, Tanya Dorff, Jessica Liu, Paul Frankel, Przemyslaw Twardowski, Savita Dandapani, Marcin Kortylewski. Immune biomarkers of response to Ra223 dichloride and stereotactic body radiation therapy in patients with oligometastatic prostate cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 677.