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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1438044
This article is part of the Research Topic The Differentiation and Reprogramming of Tumor-Associated Myeloid Cells and Therapeutic Strategies for Cancer Immunotherapy View all articles

Radiation Immunodynamics in Patients with Glioblastoma Receiving Chemoradiation

Provisionally accepted
  • 1 Department of Radiation Oncology, University of Minnesota, Minneapolis, United States
  • 2 University of Minnesota Medical School, University of Minnesota, Minneapolis, United States
  • 3 Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, United States
  • 4 Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, United States
  • 5 The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States
  • 6 The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, United States
  • 7 Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, United States
  • 8 Brain Cancer Research Program, Johns Hopkins University School of Medicine, Baltimore, United States
  • 9 Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, United States
  • 10 Department of Neurosurgery, Stanford University School of Medicine, Stanford, United States
  • 11 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States

The final, formatted version of the article will be published soon.

    This is a prospective, rigorous inquiry into the systemic immune effects of standard adjuvant chemoradiotherapy, for WHO grade 4, glioblastoma. The purpose is to identify peripheral immunologic effects never yet reported in key immune populations, including myeloid derived suppressor cells, which are critical to the immune suppressive environment of glioblastoma. We hypothesize that harmful immune-supportive white blood cells, myeloid derived suppressor cells, expand in response to conventionally fractionated radiotherapy with concurrent temozolomide, essentially promoting systemic immunity similar what is seen in chronic diseases like diabetes and heart disease. 16 patients were enrolled in a single-institution, observational, immune surveillance study where peripheral blood was collected and interrogated by flow cytometry and RNAseq. Tumor tissue from baseline assessment was analyzed with spatial proteomics to link peripheral blood findings to baseline tissue characteristics. We identified an increase in myeloid derived suppressor cells during the final week of a six-week treatment of chemoradiotherapy in peripheral blood of patients that were not alive at 2 years after diagnosis compared to those who were living. This was also associated with a decrease in CD8 + T lymphocytes that produced IFNγ, the potent anti-tumor cytokine. These data suggest that, as in chronic inflammatory disease, systemic immunity is impaired following delivery of adjuvant chemoradiotherapy. Finally, baseline investigation of myeloid cells within tumor tissue did not differ between survival groups, indicating immune surveillance of peripheral blood during adjuvant therapy may be a critical missing link to educate our understanding of the immune effects of standard of care therapy for glioblastoma.

    Keywords: Glioblastoma, Immune System, Chemoradiotherapy, Radiotherapy, brain tumor

    Received: 24 May 2024; Accepted: 12 Jul 2024.

    Copyright: © 2024 Sloan, Sen, Liu, Doucet, Blosser, Katulis, Kamson, Grossman, Holdhoff, Redmond, Quon, Lim, Eberhart, Pardoll, Hu, Ganguly and Kleinberg. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Lawrence Kleinberg, Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, United States

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