Radiotherapy-Induced Astrocyte Senescence Promotes an Immunosuppressive Microenvironment in Glioblastoma to Facilitate Tumor Regrowth.

in Advanced science (Weinheim, Baden-Wurttemberg, Germany) by Jianxiong Ji, Kaikai Ding, Bo Cheng, Xin Zhang, Tao Luo, Bin Huang, Hao Yu, Yike Chen, Xiaohui Xu, Haopu Lin, Jiayin Zhou, Tingtin Wang, Mengmeng Jin, Aixia Liu, Danfang Yan, Fuyi Liu, Chun Wang, Jingsen Chen, Feng Yan, Lin Wang, Jianmin Zhang, Senxiang Yan, Jian Wang, Xingang Li, Gao Chen

TLDR

  • The study found that some cells in the brain that were damaged by radiation became 'old' and stopped working properly. These old cells helped the cancer cells grow back by letting other cells come in to help them. The study also found that a special kind of old cell called an astrocyte was especially helpful in this process. The study used a special kind of medicine to get rid of these old cells, and it helped the cancer cells grow back less. This study is important because it shows that we might be able to use this medicine to help people with cancer who have had radiation therapy.

Abstract

Accumulating evidence suggests that changes in the tumor microenvironment caused by radiotherapy are closely related to the recurrence of glioma. However, the mechanisms by which such radiation-induced changes are involved in tumor regrowth have not yet been fully investigated. In the present study, how cranial irradiation-induced senescence in non-neoplastic brain cells contributes to glioma progression is explored. It is observed that senescent brain cells facilitated tumor regrowth by enhancing the peripheral recruitment of myeloid inflammatory cells in glioblastoma. Further, it is identified that astrocytes are one of the most susceptible senescent populations and that they promoted chemokine secretion in glioma cells via the senescence-associated secretory phenotype. By using senolytic agents after radiotherapy to eliminate these senescent cells substantially prolonged survival time in preclinical models. The findings suggest the tumor-promoting role of senescent astrocytes in the irradiated glioma microenvironment and emphasize the translational relevance of senolytic agents for enhancing the efficacy of radiotherapy in gliomas.

Overview

  • The study investigates the relationship between radiation-induced changes in the tumor microenvironment and glioma recurrence. The methodology involves cranial irradiation and senolytic agents to eliminate senescent brain cells in preclinical models. The primary objective is to determine the role of senescent astrocytes in promoting glioma progression and the potential of senolytic agents to enhance the efficacy of radiotherapy in gliomas.

Comparative Analysis & Findings

  • The study found that senescent brain cells, particularly astrocytes, facilitated tumor regrowth by enhancing the peripheral recruitment of myeloid inflammatory cells in glioblastoma. The senescence-associated secretory phenotype was identified as a mechanism by which astrocytes promoted chemokine secretion in glioma cells. The use of senolytic agents after radiotherapy substantially prolonged survival time in preclinical models, suggesting the tumor-promoting role of senescent astrocytes in the irradiated glioma microenvironment.

Implications and Future Directions

  • The findings of the study highlight the translational relevance of senolytic agents for enhancing the efficacy of radiotherapy in gliomas. Future research directions could include the development of personalized senolytic therapies based on the specific senescent populations present in individual tumors, as well as the exploration of the potential of senolytic agents to target other types of cancer.
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