Cancers, Vol. 13, Pages 5232: Radiation-Induced Fibrotic Tumor Microenvironment Regulates Anti-Tumor Immune Response

Cancers, Vol. 13, Pages 5232: Radiation-Induced Fibrotic Tumor Microenvironment Regulates Anti-Tumor Immune Response Cancers doi: 10.3390/cancers13205232 Authors: Jae-Kyung Nam Ji-Hee Kim Min-Sik Park Eun Ho Kim Joon Kim Yoon-Jin Lee High linear energy transfer (LET) radiation, such as neutron radiation, is considered more effective for the treatment of cancer than low LET radiation, such as X-rays. We previously reported that X-ray irradiation induced endothelial-to-mesenchymal transition (EndMT) and profibrotic changes, which contributed to the radioresistance of tumors. However, this effect was attenuated in tumors of endothelial-specific Trp53-knockout mice. Herein, we report that compared to X-ray irradiation, neutron radiation therapy reduced collagen deposition and suppressed EndMT in tumors. In addition to the fewer fibrotic changes, more cluster of differentiation (CD8)-positive cytotoxic T cells were observed in neutron-irradiated regrowing tumors than in X-ray-irradiated tumors. Furthermore, lower programmed death-ligand 1 (PD-L1) expression was noted in the former. Endothelial-specific Trp53 deletion suppressed fibrotic changes within the tumor environment following both X-ray and neutron radiation therapy. In particular, the upregulation in PD-L1 expression after X-ray radiation therapy was significantly dampened. Our findings suggest that compared to low LET radiation therapy, high LET radiation therapy can efficiently suppress profibrotic chan...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research