Frontiers in Immunology (Sep 2024)
Radiation immunodynamics in patients with glioblastoma receiving chemoradiation
- Lindsey Sloan,
- Lindsey Sloan,
- Lindsey Sloan,
- Lindsey Sloan,
- Lindsey Sloan,
- Lindsey Sloan,
- Rupashree Sen,
- Rupashree Sen,
- Chunnan Liu,
- Michele Doucet,
- Michele Doucet,
- Lee Blosser,
- Lee Blosser,
- Lisa Katulis,
- David O. Kamson,
- David O. Kamson,
- David O. Kamson,
- Stuart Grossman,
- Stuart Grossman,
- Matthias Holdhoff,
- Matthias Holdhoff,
- Kristin J. Redmond,
- Kristin J. Redmond,
- Harry Quon,
- Harry Quon,
- Michael Lim,
- Charles Eberhart,
- Charles Eberhart,
- Drew M. Pardoll,
- Drew M. Pardoll,
- Chen Hu,
- Chen Hu,
- Sudipto Ganguly,
- Sudipto Ganguly,
- Lawrence R. Kleinberg,
- Lawrence R. Kleinberg,
- Lawrence R. Kleinberg
Affiliations
- Lindsey Sloan
- Department of Radiation Oncology, University of Minnesota, Minneapolis, MN, United States
- Lindsey Sloan
- University of Minnesota Medical School, University of Minnesota, Minneapolis, MN, United States
- Lindsey Sloan
- Masonic Cancer Center, University of Minnesota, Minneapolis, MN, United States
- Lindsey Sloan
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Lindsey Sloan
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Lindsey Sloan
- The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Rupashree Sen
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Rupashree Sen
- The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Chunnan Liu
- Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Michele Doucet
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Michele Doucet
- The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Lee Blosser
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Lee Blosser
- The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Lisa Katulis
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- David O. Kamson
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- David O. Kamson
- Brain Cancer Research Program, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- David O. Kamson
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Stuart Grossman
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Stuart Grossman
- Brain Cancer Research Program, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Matthias Holdhoff
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Matthias Holdhoff
- Brain Cancer Research Program, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Kristin J. Redmond
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Kristin J. Redmond
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Harry Quon
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Harry Quon
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Michael Lim
- 0Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, United States
- Charles Eberhart
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Charles Eberhart
- 1Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Drew M. Pardoll
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Drew M. Pardoll
- The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Chen Hu
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Chen Hu
- 2Department of Biostatistics, Johns Hopkins University, Baltimore, MD, United States
- Sudipto Ganguly
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Sudipto Ganguly
- The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Lawrence R. Kleinberg
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Lawrence R. Kleinberg
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Lawrence R. Kleinberg
- Brain Cancer Research Program, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- DOI
- https://doi.org/10.3389/fimmu.2024.1438044
- Journal volume & issue
-
Vol. 15
Abstract
IntroductionThis 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.Methods16 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.ResultsWe 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 two 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.DiscussionThese 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
