Radiation and Cancer Biology

SS 05 - Biology 2 - Radiation and Immune Response Session I

48 - Dependency of Radiation Therapy and Combinatorial Radio-Immunotherapy Responses on the Systemic T Cell Immune Response

Sunday, October 21
5:15 PM - 5:25 PM
Location: Room 007 C/D

Dependency of Radiation Therapy and Combinatorial Radio-Immunotherapy Responses on the Systemic T Cell Immune Response
K. L. M. Chua1, E. L. L. Yeo1, X. Lin1, W. Ahamed1, P. L. Chu1, K. P. Low1, D. J. J. Poon1, E. H. W. Ong1, J. Wee1, A. Nardin2, M. Fehlings2, K. C. Soo1, and M. L. K. Chua1; 1National Cancer Centre Singapore, Singapore, Singapore, 2immunoSCAPE, Singapore, Singapore

Purpose/Objective(s): Combinatorial immune checkpoint blockade (ICB) with radiotherapy (RT) potentiates anti-tumour response via modulation of the immune microenvironment. However, detailed host-specific mechanisms underpinning dramatic clinical responses of RT-ICB are poorly understood. Here, we performed in depth characterization of the systemic immune response in circulating T cells following treatment with RT and RT-ICB.

Materials/Methods: We recruited a cohort of 29 patients with biopsy-proven metastatic cancers (10 prostate, 10 EBV+ nasopharynx, 9 others) who underwent RT (N = 13) or RT-ICB (N = 16; anti-PD1/-PDL1/-CTLA4), under a prospective observational study protocol. All patients received ablative RT (8-50 Gy in 1-5 fractions). Patient blood samples were longitudinally collected at the following timepoints: baseline, 2 d, 7 d, and 14 d post-RT/RT-ICB. Circulating T cells were deeply profiled by using a customized CyTOF panel consisting of 41 phenotypic and functional marker molecules and high-performance dimensional reduction and clustering analysis (t-SNE and PhenoGraph).

Results: Median follow-up was 3.6 mo (0.5–8 mo). At time of reporting, 26 of 29 patients had evaluable lesions; response of any kind was observed in 9 of 12 cases in the RT cohort and 12 of 14 cases in the RT-ICB cohort. However, we observed increased complete response rates at 1 mo in the RT-ICB than RT group (50% vs 8%). Additionally, we observed abscopal responses in 2 of 14 RT-ICB cases. We detected significant shifts in the CD8+ and CD4+ T cells that peaked 7 d post-RT (P <0.001). Interestingly, the majority of responses (67%) involved the expansion of a distinct immunophenotype of elevated TbetDimCD28high effector memory CD8+ and CD4+ T cells post-RT. These responses were reproduced in the RT-ICB cohort; in particular, CD28highCD27high CD4+ T cells were increased in the exceptional responders (P = 0.027). Lastly, for a patient with abscopal response, this was associated with a 25% reduction of TH2 CD4+ T cells.

Conclusion: Here, we characterized the systemic immune repertoire of circulating CD8+ and CD4+ T cells in response to RT, either alone or in combination with immunotherapy. Our data suggests that expansion of a distinct CD28highCD27high CD4+ T cell population may account for the dramatic responses to RT-immunotherapy.

Author Disclosure: K.L. Chua: Honoraria; Varian Medical Systems. Consultant; National Cancer Centre Singapore. Co-Chair Neuro Oncology Cancer Service Workgroup; National Cancer Centre Singapore. E.L. Yeo: None. X. Lin: None. W. Ahamed: None. M. Fehlings: None. M. Chua: None.

Kevin Chua, MBBS

Disclosure:
Employment
National Cancer Centre Singapore: Consultant: Employee

Compensation
National Cancer Centre Singapore: Consultant; Varian Medical Systems: Honoraria

Leadership
National Cancer Centre Singapore: Co-Chair Neuro Oncology Cancer Service Workgroup

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