Radiation and Cancer Biology

PD 11 - Biology 5 - Poster Discussion

1094 - High Dose per Fraction Radiation Therapy Increases Both Tumor-Infiltrating Lymphocytes and Suppressive Immune Cells in Prostate Cancer

Tuesday, October 23
3:09 PM - 3:15 PM
Location: Room 217 A/B

High Dose per Fraction Radiation Therapy Increases Both Tumor-Infiltrating Lymphocytes and Suppressive Immune Cells in Prostate Cancer
N. G. Nickols1, L. Lin2, N. Kane2, N. Kobayashi2, and R. E. Reiter3; 1Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, 2UCLA, Los Angeles, CA, 3Department of Urology, University of California, Los Angeles, Los Angeles, CA

Purpose/Objective(s): The use of extreme hypofractionated stereotactic body radiotherapy (SBRT) for prostate cancer is growing; the radiobiology of high dose per fraction RT is incompletely understood. We hypothesize that high dose per fraction RT will increase both tumor-infiltrating lymphocytes (TILs) and myeloid-derived suppressive cells (MDSC). The objective is to assess both the potential for immunogenic and immunosuppressive effects induced by high dose per fraction RT in prostate cancer experimental models. The long-term goal is to inform future clinical trials combining high dose per fraction RT with targeted immune therapy.

Materials/Methods: We used the syngeneic murine allograft prostate cancer models RM-1, TRAMP-C1, and MycCap, to study dynamic change of TILs and MDSC after high dose per fraction RT using flow cytometry and immunohistochemistry. RM-1 and TRAMP-C1 tumors were treated with two doses of 8 Gy separated by 8 hours, while MycCap tumors were treated with a single dose of 8 Gy, based on their relative radiosensitivities. Tumor tissue and blood were evaluated serially up to two weeks.

Results: All three syngeneic prostate cancer models demonstrated a notable increase in tumor-infiltrating MDSCs immediately after RT. This early rise of MDSCs in RM-1 tumors was largely driven by mononuclear MDSCs, whereas those in TRAMP-C1 and MycCap tumors were driven by polymorphonuclear MDSCs. Subsequent to the initial rise, MDSCs returned to baseline at day 7 after RT, and then gradually rose again at day 14. RT also induced an immediate drop of CD4 and CD8 TILs, and subsequently, a gradual rise of both cell types. For both CD4 and CD8 TILs, the fraction of cells that express PD-1 increased over time after RT, which was consistent across the different models, suggesting RT may induce preferential expansion of PD-1+ TILs. Besides local effects, RT of primary tumors also increased the fractions of MDSCs and Tregs in non-irradiated synchronous tumors, suggesting that the high dose per fraction RT also induced a systemic immune response

Conclusion: Our current hypothesis is that RT may increase infiltration of potentially tumor reactive T cells that may be suppressed by co-existing MDSCs.

Author Disclosure: N.G. Nickols: None. L. Lin: None. N. Kane: None. R.E. Reiter: None.

Nicholas Nickols, MD, PhD

Disclosure:
No relationships to disclose.

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