Radiation-induced fibrosis: Mechanisms and therapeutic strategies from an immune microenvironment perspective

Radiation-induced fibrosis (RIF) is a severe chronic complication of radiotherapy (RT) manifested by excessive extracellular matrix (ECM) components deposition within the irradiated area. The lung, heart, skin, jaw, pelvic organs and so on may be affected by RIF, which hampers body functions and quality of life. There is accumulating evidence suggesting that the immune microenvironment may play a key regulatory role in RIF. This article discussed the synergetic or antagonistic effects of immune cells and mediators in regulating RIF's development. Several potential preventative and therapeutic strategies for RIF were proposed based on the immunological mechanisms to provide clinicians with improved cognition and clinical treatment guidance. Radiation-induced fibrosis (RIF) is a chronic radiotherapy complication that manifests the over-deposition of extracellular matrix (ECM). It adversely affects the aesthetic and functional prognosis of irradiated tissues and organs. Exposure to radiation triggers a unique immune-inflammatory microenvironment, involving the recruitment of immune cells and signalling with the secretion of cell factors. The microenvironment plays a crucial role in controlling the activation of myofibroblasts and their fibrogenic responses, further regulating the progression and regression of fibrosis. Based on the immunopathogenesis, several promising anti-fibrotic therapy strategies were introduced, hoping to treat RIF accurately and effectively. image