Laboratory of Tumor Angiogenesis Initiative, Georgia Cancer Center, Augusta University, Augusta, Georgia, United States of America.
Department of Chemistry and Physics, Augusta University, Augusta, Georgia, United States of America.
PLoS One. 2021 Feb 5;16(2):e0246646. doi: 10.1371/journal.pone.0246646. eCollection 2021.
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.
胶质母细胞瘤（GBM）是中枢神经系统中一种高度血管化和侵袭性的原发性恶性肿瘤。最近的研究表明，由于治疗后耐药性和复发的发展，传统疗法联合抗血管生成疗法已经失败。先前的研究表明，肿瘤微环境（TME）中的细胞和代谢组成发生了变化。可以说，针对肿瘤细胞的治疗方法是无效的，需要重新思考如何治疗 GBM。有人假设，基于治疗方法和治疗药物，TME 相关细胞的组成将有所不同，而针对 TME 的治疗将更好地减少复发并提高生存率。因此，本研究的目的是确定在 GBM 同源模型中，不同治疗方法对 T 细胞群体、M1 和 M2 巨噬细胞极化状态以及髓系来源抑制细胞（MDSC）群体的 TME 变化。除了这些参数外，还研究了不同治疗方法对肿瘤生长和生存的影响。结果表明，TME 相关细胞的变化取决于治疗药物，TME 靶向治疗可提高 GBM 荷瘤动物的生存率。目前的 GBM 治疗方法应进行重新评估，以添加药物来防止骨髓来源细胞在 TME 中积累，或防止免疫抑制性髓样细胞影响导致替代血管生成、胶质瘤干细胞复活和复发。与联合治疗相比，序贯策略可能更有利于靶向 TME 相关细胞。
