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

Autor: Ali S; Laboratory of Tumor Angiogenesis Initiative, Georgia Cancer Center, Augusta University, Augusta, Georgia, United States of America., Borin TF; Laboratory of Tumor Angiogenesis Initiative, Georgia Cancer Center, Augusta University, Augusta, Georgia, United States of America., Piranlioglu R; Laboratory of Tumor Angiogenesis Initiative, Georgia Cancer Center, Augusta University, Augusta, Georgia, United States of America., Ara R; Laboratory of Tumor Angiogenesis Initiative, Georgia Cancer Center, Augusta University, Augusta, Georgia, United States of America., Lebedyeva I; Department of Chemistry and Physics, Augusta University, Augusta, Georgia, United States of America., Angara K; Department of Pediatrics and Human Development, Michigan State University, Grand Rapids, Michigan, United States of America., Achyut BR; Winship Cancer Institute, Emory University, Atlanta, Georgia, United States of America., Arbab AS; Laboratory of Tumor Angiogenesis Initiative, Georgia Cancer Center, Augusta University, Augusta, Georgia, United States of America., Rashid MH; Laboratory of Tumor Angiogenesis Initiative, Georgia Cancer Center, Augusta University, Augusta, Georgia, United States of America.; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2021 Feb 05; Vol. 16 (2), pp. e0246646. Date of Electronic Publication: 2021 Feb 05 (Print Publication: 2021).
DOI: 10.1371/journal.pone.0246646
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje