Radiation-Induced Alterations in the Recurrent Glioblastoma Microenvironment: Therapeutic Implications.
Radiation-Induced Alterations in the Recurrent Glioblastoma Microenvironment: Therapeutic Implications.
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DOI：
10.3389/fonc.2018.00503
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发表时间：
2018
影响因子：
4.7
通讯作者：
Burns TC
中科院分区：
文献类型：
--
作者：
Gupta K;Burns TC
胶质母细胞瘤（GBM）是致命的，尽管有包括放疗（RT）在内的最佳治疗方法，但中位生存期仅为1年多。尽管越来越多的证据表明，RT诱导的脑微环境改变有助于复发性GBM侵袭性，但先前脑RT对复发性肿瘤的影响尚不清楚。肿瘤微环境通过支持肿瘤生长的基质细胞直接或间接影响恶性细胞。据报道，细胞外基质（ECM）的改变、血管异常、缺氧和炎症可促进肿瘤的侵袭性，而这种侵袭性可能因先前的放疗而加剧。先前的放疗可能对小胶质细胞和脑浸润单核细胞有长期影响，导致细胞因子信号传导和ECM的持续改变。肿瘤促进中枢神经系统损伤反应在肿瘤微环境中重现，并在先前的辐射后增强，影响中枢神经系统的细胞表型、增殖和浸润。由于放疗对GBM治疗至关重要，但实质上改变了肿瘤微环境，我们在这里回顾了与靶向GBM微环境的致瘤性特征相关的挑战、知识差距和治疗机会。我们认为，从rt诱导的肿瘤微环境变化中获得的见解可能为靶向机制（如细胞衰老）提供了机会，这些机制可能会促进GBM侵袭性在先前辐射的微环境中放大。
Glioblastoma (GBM) is uniformly fatal with a median survival of just over 1 year, despite best available treatment including radiotherapy (RT). Impacts of prior brain RT on recurrent tumors are poorly understood, though increasing evidence suggests RT-induced changes in the brain microenvironment contribute to recurrent GBM aggressiveness. The tumor microenvironment impacts malignant cells directly and indirectly through stromal cells that support tumor growth. Changes in extracellular matrix (ECM), abnormal vasculature, hypoxia, and inflammation have been reported to promote tumor aggressiveness that could be exacerbated by prior RT. Prior radiation may have long-term impacts on microglia and brain-infiltrating monocytes, leading to lasting alterations in cytokine signaling and ECM. Tumor-promoting CNS injury responses are recapitulated in the tumor microenvironment and augmented following prior radiation, impacting cell phenotype, proliferation, and infiltration in the CNS. Since RT is vital to GBM management, but substantially alters the tumor microenvironment, we here review challenges, knowledge gaps, and therapeutic opportunities relevant to targeting pro-tumorigenic features of the GBM microenvironment. We suggest that insights from RT-induced changes in the tumor microenvironment may provide opportunities to target mechanisms, such as cellular senescence, that may promote GBM aggressiveness amplified in previously radiated microenvironment.
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