Insights into the Immunoprofile of Cutaneous Radiation Fibrosis

Summary: Cutaneous radiation fibrosis (CRF) is a significant cause of patient morbidity. Few studies have examined the clinical, histopathologic, and immunohistochemical (IHC) spectrum of CRF in human tissue. We performed dual IHC for Type 1- and Type 2-helper T-cell populations (Th1: CD4+TBET+ and Th2: CD4+GATA3+, respectively) in 18 cases (2016-2023) with available clinical histories. Th1 and Th2 subpopulations were quantified for the average positively stained cells in three high power fields (hpf). The average patient age was 68.2 years. Other than sex (P= 0.0491), there were no significant clinical differences when stratified by < 36 months and ≥ 36 months from last radiation exposure to biopsy-proven CRF. Quantitative analysis revealed significant increases in the average CD4+ T cell density at < 36 months and ≥ 36 months (13.4 vs 39.0 cells/hpf, p = 0.043) and the Th1 subpopulation (0.6 vs 5.6 cells/hpf, p = 0.005), without significant difference in the Th2 response (3.1 vs 5.8 cells/hpf; p = 0.344). While high dose irradiation has been implicated in reduction of Th1 cell function in other tissues, this study suggests Th1 cells may play a key role in CRF. Our study provides insights that may facilitate advanced, immune cell-focused interventions for CRF.