High proportion of circulating CD8 + CD28- senescent T cells is an independent predictor of distant metastasis in nasopharyngeal canrcinoma after radiotherapy

Background: Nasopharyngeal carcinoma (NPC) is a kind of epithelial carcinoma that is common in East and Southeast Asia. Distant metastasis after radiotherapy remains the main cause of treatment failure and preradiotherapy immune system function can influence prognosis. Our study aimed to identify immune-related prognostic factors for NPC after radiotherapy and establish a prognostic model to predict progression-free survival (PFS) and distant metastasis-free survival (DMFS).

Methods: We enrolled NPC patients and divided them into training and validation cohorts with follow-up. We collected clinical information and investigated immune cells, EBV DNA and cytokines in the peripheral blood of NPC patients before radiotherapy and EBV DNA after radiotherapy. Among these immune cells, we included CD8⁺CD28^- T cells, which are a unique T-cell immunosenescent subset that increases in human peripheral blood with increasing age and declining immune function. Based on the detection results and clinical information, we utilized Cox regression and least absolute shrinkage and selection operator (LASSO) regression to screen the PFS and DMFS prognostic factors and build nomograms to predict the PFS and DMFS of NPC. We also verified the results in the validation set.

Results: Three factors associated with PFS were selected: proportion of CD8⁺CD28^- T cells posttreatment EBV and N stage. Three factors associated with DMFS were screened: proportion of CD8⁺CD28^- T cells, posttreatment EBV and N stage. CD8⁺CD28^- T cells are correlated with systemic inflammation and posttreatment immunosuppression. The C-indexes were 0.735 and 0.745 in the training and validation cohorts for predicting PFS. For DMFS, the C-indexes were 0.793 and 0.774 in the training and validation cohorts.

Conclusions: The pretreatment proportion of CD8⁺CD28^- T cells is a candidate prognostic biomarker for NPC after radiotherapy. The constructed nomogram models based on CD8⁺CD28^- T cells have good predictive value.