Mitochondrial function changes in T cell subsets during radiotherapy for patients with nasopharyngeal carcinoma

Mitochondrial dysfunction-mediated T cell exhaustion is associated with the efficacy of tumor therapy; however, the effect of radiotherapy (RT) on the mitochondrial function of peripheral blood immune cells remains still unclear. Therefore, the current study aimed to determine mitochondrial function indicators in immune cells, in particular mitochondrial mass (MM) and mitochondrial membrane potential (MMP), to assess the dynamic changes of immune status in patients with nasopharyngeal carcinoma (NPC) during RT. Peripheral venous blood was collected from patients with locally advanced NPC at day 1 pre-RT, at the 10th fraction of RT and within 2 days after RT. Based on a novel immunofluorescence technique, flow cytometry was used to assess the proportion of lymphocytes and their subsets in peripheral blood and the mitochondrial indexes, MM and low MMP (MMP^low). Univariate and multivariate logistic regression analyses were performed to evaluate the clinical factors associated with the efficacy of RT. A total of 27 patients were enrolled. After RT, lymphocyte count (P<0.05) and the proportion of CD4⁺ T cells (P<0.05) demonstrated a downward trend. In addition, the proportion of CD4⁺ memory-effector T (Tem; P<0.05) cells and CD8⁺ Tem cells (P=0.005) significantly increased during RT. No significant changes were demonstrated for MM in CD4⁺ effector T (Te) cells, whilst MMP^low was significantly reduced (P=0.047). However, the mitochondrial function of CD8⁺ T cells did not significantly change. Multivariate logistic regression analysis revealed that lymphocyte count [odds ratio (OR), 47.317; 95% confidence interval (CI), 1.240-1806.065] and MMP^low in CD4⁺ Te cells (OR, 0.889; 95% CI, 0.792-0.997) were independent factors that could affect clinical efficacy. Receiver operating characteristic curve analysis demonstrated that the area under the curve values for MMP^low in CD4⁺ T cells, lymphocyte count and their combination were 0.72 (P=0.13), 0.69 (P=0.19) and 0.89 (P=0.0073), respectively. These findings suggest that RT could inhibit immune cells in peripheral blood. However, this treatment approach could activate the memory cell subsets of immune cells and enhance the MMP of effector CD4⁺ T cells. Therefore, the evaluation of mitochondrial function in lymphocytes could be used as a predictor of RT efficacy in patients with locally advanced NPC.