Radiation and Cancer Biology

PD 11 - Biology 5 - Poster Discussion

1095 - Effective Abscopal Response is Dependent on Optimal Radiation Dose and Sequencing With Anti-PD1 therapy.

Tuesday, October 23
3:15 PM - 3:21 PM
Location: Room 217 A/B

Effective Abscopal Response is Dependent on Optimal Radiation Dose and Sequencing With Anti-PD1 therapy.
T. Nasti1, S. Im1, H. T. Kissick2, C. Daugherty1, D. Lawson3, R. Ahmed1, and M. K. Khan4; 1Department of Microbiology/Immunology, Emory University, Atlanta, GA, 2Department of Urology, Emory University, Atlanta, GA, 3Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, 4Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA

Purpose/Objective(s): Radiotherapy sometimes leads to remission at sites outside the field, in a phenomenon termed the “abscopal effect.” T cells, in particular CD8 T cells are believed to mediate this response. The purpose of this study was to understand how radiotherapy dose and sequencing relative to anti-PD1 therapy affects the abscopal response.

Materials/Methods: To answer our question, we developed a human equivalent syngeneic mouse model established in C57/BL6 mice by injecting B16F10GP melanoma cells in both flanks. One flank was irradiated with different radiation doses, and tumors measured every 2-3 days. For immunotherapy, anti-PD1 antibody (muDX400) was used.

Results: There was a significant delay in tumor growth of the radiated site, as well as the distant non-irradiated tumor site depending on the radiation dose used. The 10 Gy was much more effective in inducing the abscopal response compared to single doses of 2, 5 or 20 Gy. CD8+ T cells showed increased proliferative capacity in the tumor using single 10 Gy radiation dose as shown by percent Ki67+PD1+ CD8+ T cells. The frequency of antigen specific CD8+ T cells also increased in both irradiated and non-irradiated tumors with the 10 Gy group, compared with other groups. Combination of anti-PD1 (muDX400) with radiation was more effective with 10 Gy than other radiation doses. The sequence of radiation followed with anti-PD1 therapy was more effective than radiation following anti-PD1 therapy. RNA seq data on exhausted (CD8+Tim3+CD73-) and stem cell like (CD8+Tim3-CD73+) cells from untreated, radiation, anti-PD1 alone or combination groups showed radiation induces interferon signaling while anti-PD1 therapy affects cell cycle genes. The combo showed changes in both gene subsets.

Conclusion: Our findings indicate that optimal radiation dose and sequence with PD1 is necessary for optimal abscopal response due to effect on stem cell like CD8+ T cells. This study will provide a stage for upcoming clinical trial designs, regarding optimal radiation dose and sequencing of radiation and anti-PD1 therapy.

Author Disclosure: T. Nasti: None. S. Im: None. H.T. Kissick: None. D. Lawson: None. R. Ahmed: Research Grant; Merck. Patent/License Fees/Copyright; Emory University. M.K. Khan: Research Grant; Merck.

Tahseen Nasti, PhD

Disclosure:
No relationships to disclose.

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