University of Minnesota Radiation Oncology Clinic University Campus Minneapolis, MN
S. Mishra1, M. Berkseth2, L. Golden1, K. B. Bergerud2, J. Wieworka3, N. Sando1, J. Lawrence4, L. Chen5, C. Ozutemiz6, E. Neil7, S. Ganguly8, L. R. Kleinberg9, K. E. Dusenbery1, A. Venteicher10, J. Yuan11, S. A. Terezakis1, and L. Sloan1; 1University of Minnesota: Department of Radiation Oncology, Minneapolis, MN, 2University of Minnesota, Minneapolis, MN, 3M Health Fairview, Minneapolis, MN, 4Masonic Cancer Center, Minneapolis, MN, 5University of Minnesota: Department of Laboratory Medicine and Pathology, Minneapolis, MN, 6University of Minnesota: Department of Radiology, Minneapolis, MN, 7University of Minnesota: Department of Neurology, Minneapolis, MN, 8The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 9Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, MD, 10University of Minnesota: Department of Neurosurgery, Minneapolis, MN, 11Department of Radiation Oncology, University of Minnesota Medical School, Minneapolis, MN
Purpose/Objective(s): Radiotherapy (RT) can hinder systemic anti-cancer immune responses via myeloid-derived suppressor cells (MDSCs). MDSCs suppress anti-tumor immunity and are associated with a poor prognosis. Recent studies in glioma patients indicate that conventionally fractionated RT increases MDSCs while hypofractionated RT decreases MDSCs. The impact of RT on MDSC-mediated immune response for benign meningioma is unknown. We hypothesized that conventional radiotherapy for patients with meningioma would increase the frequency of MDSCs and enhance immunosuppressive cytokine expression. To address this hypothesis, we aimed to compare MDSCs and cytokine expression before and after conventional RT in patients with meningiomas. Materials/
Methods: Patients with radiation-naïve, intracranial meningioma treated with conventional RT were enrolled in this prospective, IRB approved study. Exclusion criteria included presence of significant anemia, thrombocytopenia, pregnancy, incarceration, or COVID-19. Peripheral blood was drawn before the first RT treatment and during the last week of RT. Flow cytometry was used to identify frequencies of MDSC subsets (M-MDSC, G-MDSC, eMDSC) and immunomodulatory cytokine expression (IL-10, TGF-ß, and IFN-?+). MDSC subtype frequencies (%MDSC) and cytokine frequency/intensity were compared before and after RT with paired Student’s t-tests. Results: 7 patients received conventionally fractionated RT, with prescription doses ranging from 4860 to 6000 cGy. The median age was 59 years (range 30-76) and 6 were male. Of the 7 tumors, 2 were WHO grade 1, 2 were WHO grade 2, and 3 were imaging diagnosed. The %MDSC of non- lymphocytes significantly decreased following RT (27.3% ± 14.9% vs. 12.3% ± 6.6%, p = 0.005). The %MDSC of CD11b+/CD33+ cells from pre-RT (34.1% ± 21.5%) to post-RT (15.0% ± 9.1%, p = 0.008). The distribution of eMDSC, M-MDSC, and G-MDSC remained unchanged post-RT. There was no overall difference in the expression frequency of IL-10, TGF-ß, and IFN-? post-RT. However, the geometric mean fluorescence intensity (GFMI) of TGF-ß significantly increased after RT (2214.4 ± 752.4 vs. 3457.7 ± 1168.0, p = 0.02). No significant differences in GFMI of IL-10 or IFN-? were measured post-RT compared to baseline. Conclusion: Preliminary results suggest conventional RT reduces the percentage of MDSCs in peripheral blood from meningioma patients, contrary to findings from patients with malignant brain tumors. The increased TGF-ß expression intensity in post-RT samples highlights the complexity of radiation-induced immunomodulatory signaling. Understanding the unique impact RT has on MDSC subsets and signaling in benign and malignant brain tumors may aid in the identification of pathways and responses that inhibit MDSC-driven immunosuppression and radio resistance. Work is ongoing to expand our study population and evaluate associations with tumor control and outcome.
