The Effects of Adjuvant Chemoradiotherapy (CRT) on Myeloid-Derived Suppressor Cell (MDSC) Subsets in Glioblastoma (GBM)

Abstract

GBM continues to be a diagnosis with an exceedingly low survival rate despite standard therapy of resection followed by concurrent CRT. MDSC, immunosuppressive myeloid cells that aid immune system evasion by the tumor, expand during fractionated RT. To date, little is known about the effects of CRT on MDSC subsets. The goal of our pilot study is to compare peripheral blood MDSC subset frequency in patients (pts) undergoing CRT. We hypothesize that the pro-tumor, monocytic MDSC (M-MDSC) subset increases following CRT. Pts over the age of 18 yo with a new diagnosis of GBM from a single institution participated in the study between 7/2022 -1/2023. Exclusion criteria included prior history of brain RT. Baseline peripheral blood samples were collected within one week prior to CRT start and post-CRT samples were collected within the last week of CRT. Peripheral blood mononuclear cells (PBMC) were isolated from whole blood and freshly stained for intracellular flow cytometric analyses. Total MDSC (singlet, viable, non-lymphocyte, CD11b+CD33+ HLA-DR- cells) and subsets (M-MDSC, granulocytic (G-MDSC), and early MDSC (eMDSC)) were identified. Percent frequency (%fx) of total and MDSC subsets as well as MDSC activation status (n = 3) (interleukin (IL)-10, transforming growth factor-β (TGF-β), interferon gamma (IFNγ)) was compared before and after CRT. The average age of pts receiving CRT (n = 4) was 70 yo. Fractionated RT consisted of CF RT (n = 2), 6000 cGy in 30 fractions, and HF RT (n = 2), 4005 cGy in 15 fractions. All pts received concurrent chemotherapy with temozolomide. The %fx of MDSC of non-lymphocytes started at 29.2% prior to CRT and decreased to 9.9% at the end of CRT. The fold change of %fx of total MDSC in CF RT and HF RT was 0.39 and 0.29, respectively. The mean change in %fx of MDSC subsets before and after CRT are shown in Table 1. The mean %fx of TGF-β-expressing MDSC in all GBM pts increased by 3.5% after CRT. The mean IFNγ+ MDSC %fx for all GBM pts decreased after CRT from 24.2% to 16.2% with a corresponding decrease in geometric mean fluorescence intensity (GMFI). The mean %fx of IL-10+ MDSC decreased by 1.5% at the end of CRT with a decrease in GMFI from 5550 to 1806. In this limited dataset of pts with GBM receiving standard of care adjuvant therapy, we identified an expansion in the eMDSC and decrease in the M-MDSC subsets. These early results suggest HF RT may promote immunity that is more supportive of anti-tumor function, with a lesser increase in fold change of total MDSC after CRT. A more detailed understanding of the effect of RT on myeloid subpopulations is essential to addressing immune suppression in pts with GBM.