The clinical manifestations and molecular pathogenesis of radiation fibrosis.

Advances in radiation techniques have enabled the precise delivery of higher doses of radiotherapy to tumours, while sparing surrounding healthy tissues. Consequently, the incidence of radiation toxicities has declined, and will likely continue to improve as radiotherapy further evolves. Nonetheless, ionizing radiation elicits tissue-specific toxicities that gradually develop into radiation-induced fibrosis, a common long-term side-effect of radiotherapy. Radiation fibrosis is characterized by an aberrant wound repair process, which promotes the deposition of extensive scar tissue, clinically manifesting as a loss of elasticity, tissue thickening, and organ-specific functional consequences. In addition to improving the existing technologies and guidelines directing the administration of radiotherapy, understanding the pathogenesis underlying radiation fibrosis is essential for the success of cancer treatments. This review integrates the principles for radiotherapy dosimetry to minimize off-target effects, the tissue-specific clinical manifestations, the key cellular and molecular drivers of radiation fibrosis, and emerging therapeutic opportunities for both prevention and treatment.

CD8+ Tumor-Infiltrating Lymphocyte Abundance Is a Positive Prognostic Indicator in Nasopharyngeal Cancer.

PURPOSE: Tumor-infiltrating lymphocytes (TIL) are immune cell populations found within tumors, critical in the antigen-specific host immune response. In this study, we aimed to elucidate the prognostic significance of CD3+, CD4+, and CD8+ TILs in nasopharyngeal cancer (NPC). EXPERIMENTAL DESIGN: Immune cell infiltration was quantified in NPC samples (n = 50) using RNA-sequencing (RNA-seq) data based on rearranged T-cell receptor (TCR) reads and the Estimation of Stromal and Immune cells in malignant tumors using expression data (ESTIMATE) immune score tool. The differential abundances of TIL subset populations were also characterized through IHC staining of formalin-fixed, paraffin-embedded samples from a training cohort (n = 35), which was a subset of the RNA-seq cohort (n = 50). RESULTS: In the RNA-seq cohort, patients with higher rearranged TCR reads experienced superior 5- and 10-year overall survival (OS; P < 0.001), and disease-free survival (DFS; P < 0.001). Similarly, patients with higher ESTIMATE immune scores experienced superior 5- and 10-year OS (P = 0.024) and DFS (P = 0.007). In the training cohort, high abundances of CD8+ TILs were significantly associated with improved 5- and 10-year OS (P = 0.003) and DFS (P = 0.005). These findings were corroborated in an independent validation cohort (n = 84), and combined analysis of the training and validation cohorts [n = 119 (35+84)], which further demonstrated improved 5- and 10-year survival in terms of locoregional control (P < 0.001) and distant metastasis (P = 0.03). CONCLUSIONS: Taken together, our study highlights the prognostic value of CD8+ TILs in NPC, and the potential of future investigations into cellular-based immunotherapies employing CD8+ lymphocytes.