Changes in the tumor microenvironment and outcome for TME-targeting therapy in glioblastoma: A pilot study

• Authors: Sehar Ali, Augusta University; Thaiz F Borin, Augusta University; Raziye Piranlioglu, Augusta University; Roxan Ara, Augusta University; Iryna Lebedyeva, Augusta University; Kartik Angara, Michigan State University; Bhagelu R Achyut, Emory University; Ali Syed Arbab, Augusta University; Mohammad H Rashid, Augusta University
• Journal Title: PLOS ONE
• Volume: Volume 16, Number 2
• Publisher: PUBLIC LIBRARY SCIENCE | 2021-02-05, Pages e0246646-e0246646
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1371/journal.pone.0246646
• Subjects: Health Sciences, Oncology; Chemistry, General; Physics, General
• Keywords: Science & Technology; Multidisciplinary Sciences; Science & Technology - Other Topics; STIMULATING FACTOR-1 RECEPTOR; INFILTRATING MYELOID CELLS; MARROW-DERIVED CELLS; RECURRENT GLIOBLASTOMA; SELECTIVE INHIBITOR; MDSC INFILTRATION; SUPPRESSOR-CELLS; VASCULAR MIMICRY; ANIMAL-MODEL; CANCER

Abstract

Glioblastoma (GBM) is a hypervascular and aggressive primary malignant tumor of the central nervous system. Recent investigations showed that traditional therapies along with antiangiogenic therapies failed due to the development of post-therapy resistance and recurrence. Previous investigations showed that there were changes in the cellular and metabolic compositions in the tumor microenvironment (TME). It can be said that tumor cell-directed therapies are ineffective and rethinking is needed how to treat GBM. It is hypothesized that the composition of TME-associated cells will be different based on the therapy and therapeutic agents, and TME-targeting therapy will be better to decrease recurrence and improve survival. Therefore, the purpose of this study is to determine the changes in the TME in respect of T-cell population, M1 and M2 macrophage polarization status, and MDSC population following different treatments in a syngeneic model of GBM. In addition to these parameters, tumor growth and survival were also studied following different treatments. The results showed that changes in the TME-associated cells were dependent on the therapeutic agents, and the TME-targeting therapy improved the survival of the GBM bearing animals. The current GBM therapies should be revisited to add agents to prevent the accumulation of bone marrow-derived cells in the TME or to prevent the effect of immune-suppressive myeloid cells in causing alternative neovascularization, the revival of glioma stem cells, and recurrence. Instead of concurrent therapy, a sequential strategy would be better to target TME-associated cells.