Abstract 527: High-dimensional profiling of the systemic immune response informs on optimal sequencing of radiotherapy (RT) and immune checkpoint blockade (ICB)

Background: Combinatorial RT-ICB potentiates anti-tumour reactivity by modulating the immune response. We therefore performed in-depth phenotypic profiling of the systemic T cell compartment following treatment with RT-ICB. Methods: We recruited 20 patients with biopsy-proven metastatic renal cell and non-small cell lung carcinoma, who were treated with a sandwich regime of ICB-RT-ICB under a prospective observational study protocol, and compared against a RT alone-treated cohort (N=10). All patients received ablative RT (8-50Gy/1-5fr) for oligoprogression and/ or local palliation. Blood samples were longitudinally collected at pre-RT, 14 d post-RT and cycle 2 ICB post-RT. Deep T cell profiling was performed by mass cytometry using a customised 41 parameter panel, together with high dimensional analysis tools. Results: Median follow-up of the overall cohort was 18mo; median duration of ICB received in the ICB-RT-ICB arm was 15mo. We observed significant diversity of the systemic T cell repertoire between patients at baseline, and this corresponded to significant interpatient heterogeneity in T cell responses specific to the central/ effector memory, EMRA and Treg subsets post-RT. Dramatic local response (complete response at 1 mo post-RT) was significantly higher in the ICB-RT-ICB cohort compared to the RT alone cohort (12/20 vs 1/10, P Conclusions: Here, we observed changes in the T cell phenotypes that varied remarkably across all patients following RT. We further highlight a RT-dependent T cell proliferation amongst all RT-ICB-treated patients that was further enhanced by ICB in prior responders. This immune phenomenon may account for the dramatic responses to combinatorial treatment, and informs on optimal sequencing strategies for combining RT and ICB. Citation Format: Kevin L. Chua, Michael Fehlings, Pek Lim Chu, Xiao-Tian Lin, Eugenia Yeo, Kar Perng Low, Dennis Poon, Enya Ong, Wai Yee Woo, Joseph Wee, Alessandra Nardin, Gopalakrishna Iyer, Daniel S. Tan, Kee Chee Soo, Evan Newell, Melvin Chua. High-dimensional profiling of the systemic immune response informs on optimal sequencing of radiotherapy (RT) and immune checkpoint blockade (ICB) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 527.