Endemic nasopharyngeal carcinoma (NPC) is associated with persistent Epstein Barr Virus (EBV) infection. Radiotherapy (RT) is standard-of-care for NPC, where clearance of EBV DNA in plasma is a recognized predictor of response. The relationship between post-RT clearance of EBV and concomitant changes in circulating immune cell populations in blood is not known.
In this study, serial blood samples were prospectively collected from 24 NPC patients before, during and post-RT, and peripheral blood mononuclear cells (PBMCs) were analysed with multiplex flow cytometry to assess the frequency of T cell subsets according to >20 markers of differentiation, co-signalling and chemotaxis. Sera were analysed for the number of EBV DNA copies by PCR, and patients were classified either as having cleared or not cleared EBV post-RT.
We observed that patients with EBV clearance demonstrated a lower frequency of PD1+ CD8 +T cells as well as CXCR3+ CD8+ T cells during and post-RT when compared to patients with no EBV clearance. Most notably, these patients showed a temporal increase in frequencies of CD8+ T cells expressing the chemo-attractant receptors CCR1, 4 and/or 5 upon RT, which was not observed in patients with no EBV clearance. The increase in frequency of CCR+ CD8+ T cells was accompanied by a drop in frequency of naïve CD8+ T cells and an increase in frequency of OX40+CD8+ T cells. Moreover, blood of non-recurrent NPC patients contained higher quantities of CCL14 and CCL15, constituting ligands for CCR1 and CCR5, prior to RT when compared to recurrent NPC patients.
Our findings suggest that plasma clearance of EBV DNA post-RT is preceded by increased frequencies of CCR1, 4 and/or 5+ CD8+ T cells, potentially serving as a predictor for EBV clearance in NPC patients, which requires validation in larger cohorts.
Erasmus MC.
Erasmus MC.
All authors have declared no conflicts of interest.