Macrophage plays an important role in homeostasis and immunity, and dysfunctional macrophage polarization is believed to be associated with the pathogenesis of tissue fibrosis and tumor progression. Colony stimulating factor-1 (CSF-1), a polypeptide chain cytokine, through its receptor (CSF-1R) regulates the differentiation of macrophages. Recently, the promising therapeutic potential of CSF-1/CSF-1R signaling pathway inhibition in cancer treatment is widely used. Furthermore, inhibition of CSF-1/CSF-1R signaling combined with radiotherapy has been extensively studied to reduce immunosuppression and promote abscopal effect. In addition, cumulative evidence demonstrated that M2 phenotype macrophage is dominant in tissue fibrosis and the inhibition of CSF-1/CSF-1R signaling pathway ameliorated pulmonary fibrosis, including radiation-induced lung fibrosis. Herein, we provide a comprehensive review of the CSF-1/CSF-1R signaling pathway in radiotherapy, with a focus on advances in macrophage-targeted strategies in the treatment of cancer and pulmonary fibrosis.

The glutathione S-transferase P1(GSTP1) is an isoenzyme in the glutathione-S transferases (GSTs) enzyme system, which is the most abundant GSTs expressed in adult lungs. Recent research shows that GSTP1 is closely related to the regulation of cell oxidative stress, inhibition of cell apoptosis and promotion of cytotoxic metabolism. Interestingly, there is evidence that GSTP1 single nucleotide polymorphisms (SNP) 105Ile/Val related to the risk of radiation induced lung injury (RILI) development, which strongly suggests that GSTP1 is closely associated with the occurrence and development of RILI. In this review, we discuss our understanding of the role of GSTP1 in RILI and its possible mechanism.

Radiotherapy is applied in about 70% patients with tumors, yet radioresistance of tumor cells remains a challenge that limits the efficacy of radiotherapy. Ferroptosis, an iron-dependent lipid peroxidation regulated cell death, is involved in the development of a variety of tumors. Interestingly, there is evidence that ferroptosis inducers in tumor treatment can significantly improve radiotherapy sensitivity. In addition, related studies show that Glutathione S-transferase P1 (GSTP1) is closely related to the development of ferroptosis. The potential mechanism of targeting GSTP1 to inhibit tumor cells from evading ferroptosis leading to radioresistance has been proposed in this review, which implies that GSTP1 may play a key role in radiosensitization of lung cancer via ferroptosis pathway.

Background: Radiation-induced lung injury (RILI) often occurs during clinical chest radiotherapy and acute irradiation from accidental nuclear leakage. This study explored the role of monophosphoryl lipid A (MPLA) in RILI. Materials and Methods: The entire thoracic cavity of C57BL/6N mice was irradiated at 20 Gy with or without pre-intragastric administration of MPLA. HE staining, Masson trichrome staining, and TUNEL assay were used to assess lung tissue injury after treatment. The effect of irradiation on the proliferation of MLE-12 cells was analyzed using the Clonogenic assay. The effect of MPLA on the apoptosis of MLE-12 cells was analyzed using flow cytometry. Expression of γ-H2AX and epithelial-mesenchymal transition (EMT) markers in MLE-12 cells was detected by immunofluorescence and Western blot, respectively. Results: MPLA attenuated early pneumonitis and late pulmonary fibrosis after thoracic irradiation and reversed radiation-induced EMT in C57 mice. MPLA further promoted proliferation and inhibited apoptosis of irradiated MLE-12 cells in vitro. Mechanistically, the radioprotective effect of MPLA was mediated by exosomes secreted by stimulated macrophages. Macrophage-derived exosomes modulated DNA damage in MLE-12 cells after irradiation. MPLA promoted the polarization of RAW 264.7 cells to the M1 phenotype. The exosomes secreted by M1 macrophages suppressed EMT in MLE-12 cells after irradiation. Conclusion: MPLA is a novel treatment strategy for RILI. Exosomes derived from macrophages are key to the radioprotective role of MPLA in RILI.

Radiotherapy is an important strategy for NSCLC. However, although a variety of comprehensive radiotherapy‐based treatments have dominated the treatment of NSCLC, it cannot be avoided to overcome the growing radioresistance during radiotherapy. The purpose of this study was to elucidate the radiosensitizing effects of NSCLC via knockdown GTSE1 expression and its mechanism. Experiments were performed by using multiple NSCLC cells such as A549, H460 and H1299. Firstly, we found GTSE1 conferred to radioresistance via clonogenic assay and apoptosis assay. Then, we detected the level of DNA damage through comet assay and γH2AX foci, which we could clearly observe knockdown GTSE1 enhance DNA damage after IR. Furthermore, through using laser assay and detecting DNA damage repair early protein expression, we found radiation could induce GTSE1 recruited to DSB site and initiate DNA damage response. Our finding demonstrated that knockdown GTSE1 enhances radiosensitivity in NSCLC through DNA damage repair pathway. This novel observation may have therapeutic implications to improve therapeutic efficacy of radiation.

Radiotherapy is one of the most important treatments for chest tumours. Although there are plenty of strategies to prevent damage to normal lung tissues, it cannot be avoided with the emergence of radiation‐induced lung injury. The purpose of this study was to investigate the potential radioprotective effects of glucosamine, which exerted anti‐inflammatory activity in joint inflammation. In this study, we found glucosamine relieved inflammatory response and structural damages in lung tissues after radiation via HE staining. Then, we detected the level of epithelial‐mesenchymal transition marker in vitro and in vivo, which we could clearly observe that glucosamine treatment inhibited epithelial‐mesenchymal transition. Besides, we found glucosamine could inhibit apoptosis and promote proliferation of normal lung epithelial cells in vitro caused by radiation. In conclusion, our data showed that glucosamine alleviated radiation‐induced lung injury via inhibiting epithelial‐mesenchymal transition, which indicated glucosamine could be a novel potential radioprotector for radiation‐induced lung injury.