Cancer-associated fibroblasts (CAFs) are important cells of the tumor microenvironment that can communicate with tumor cells through various mechanisms. Recently, increasing studies have found that exosomes transmit biological information by carrying microRNAs, lncRNAs, proteins, metabolites, and other substances, and thus exert biological and therapeutic effects. CAF-secreted exosomes can also affect the tumor phenotype, while the exosomes released by tumor cells can activate CAFs. Here, we review the role of exosomes in the crosstalk between CAFs and tumor cells and elaborate its mechanism.

Background: Radiation-induced lung injury (RILI) is a prevalent complication of thoracic radiotherapy in cancer patients. A comprehensive understanding of the underlying mechanisms of RILI is essential for the development of effective prevention and treatment strategies. Methods: To investigate RILI, we utilized a mouse model that received 12.5 Gy whole-thoracic irradiation. The evaluation of RILI was performed using a combination of quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), histology, western blot, immunohistochemistry, RNA sequencing, and flow cytometry. Additionally, we established a co-culture system consisting of macrophages, lung epithelial cells, and fibroblasts for in vitro studies. In this system, lung epithelial cells were irradiated with a dose of 4 Gy, and we employed STING knockout macrophages. Translational examinations were conducted to explore the relationship between STING expression in pre-radiotherapy lung tissues, dynamic changes in circulating CCL2, and the development of RILI. Results: Our findings revealed significant activation of the cGAS-STING pathway and M1 polarization of macrophages in the lungs of irradiated mice. In vitro studies demonstrated that the deficiency of cGAS-STING signaling led to impaired macrophage polarization and RILI. Through RNA sequencing, cytokine profiling, and rescue experiments using a CCL2 inhibitor called Bindarit, we identified the involvement of CCL2 in the regulation of macrophage polarization and the development of RILI. Moreover, translational investigations using patient samples collected before and after thoracic radiotherapy provided additional evidence supporting the association between cGAS-STING signaling activity, CCL2 upregulation, and the development of radiation pneumonitis. Conclusions: The cGAS-STING signaling pathway plays a crucial role in regulating the recruitment and polarization of macrophages, partly through CCL2, during the pathogenesis of RILI.

Consensus International consensus on radiotherapy in metastatic non-small cell lung cancer Zhengfei Zhu, Jianjiao Ni, Xuwei Cai, Shengfa Su, Hongqing Zhuang, Zhenzhou Yang, Ming Chen, Shenglin Ma, Conghua Xie, Yaping Xu, Jiancheng Li, Hong Ge, Anwen Liu, Lujun Zhao, Chuangzhou Rao, Congying Xie, Nan Bi, Zhouguang Hui, Guangying Zhu, Zhiyong Yuan, Jun Wang, Lina Zhao, Wei Zhou, Chai Hong Rim, Arturo Navarro-Martin, Ben G. L. Vanneste, Dirk De Ruysscher, J. Isabelle Choi, Jacek Jassem, Joe Y. Chang, Lucyna Kepka, Lukas Käsmann, Michael T. Milano, Paul Van Houtte, Rafal Suwinski, Alberto Traverso, Hiroshi Doi, Yang-Gun Suh, Georges Noël, Natsuo Tomita, Roman O. Kowalchuk, Terence T. Sio, Baosheng Li, Bing Lu, Xiaolong Fu