Frequency of Peripheral CD8+ T Cells Expressing Chemo-Attractant Receptors CCR1, 4 and 5 Increases in NPC Patients with EBV Clearance upon Radiotherapy

SIMPLE SUMMARY: The post-radiotherapy (RT) clearance of tumor-derived plasma EBV DNA is associated with a better prognosis in patients with nasopharyngeal cancer (NPC). T cells may play a critical role in the clearance of plasma EBV DNA in NPC. We explored the dynamic changes in circulating T-cell profiles during RT and observed that a temporal increase in the frequency of CD8+ T cells expressing CCR1, 4 and/or 5 was associated with plasma EBV DNA clearance. Moreover, differences in the plasma levels of the corresponding chemo-attractants are related to clinical outcome. Our study demonstrated correlation between plasma EBV DNA clearance post-RT and T-cell chemotaxis, which requires validation in larger cohorts. Markers of T-cell chemotaxis may be prognostic biomarkers in patients with NPC undergoing RT. ABSTRACT: Radiotherapy (RT) is the standard-of-care for Epstein–Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), where the post-RT clearance of plasma EBV DNA is prognostic. Currently, it is not known whether the post-RT clearance of plasma EBV DNA is related to the presence of circulating T-cell subsets. Blood samples from NPC patients were used to assess the frequency of T-cell subsets relating to differentiation, co-signaling and chemotaxis. Patients with undetectable versus detectable plasma EBV DNA levels post-RT were categorized as clearers vs. non-clearers. Clearers had a lower frequency of PD1+CD8+ T cells as well as CXCR3+CD8+ T cells during RT compared to non-clearers. Clearers exclusively showed a temporal increase in chemo-attractant receptors CCR1, 4 and/or 5, expressing CD8+ T cells upon RT. The increase in CCR-expressing CD8+ T cells was accompanied by a drop in naïve CD8+ T cells and an increase in OX40+CD8+ T cells. Upon stratifying these patients based on clinical outcome, the dynamics of CCR-expressing CD8+ T cells were in concordance with the non-recurrence of NPC. In a second cohort, non-recurrence associated with higher quantities of circulating CCL14 and CCL15. Collectively, our findings relate plasma EBV DNA clearance post-RT to T-cell chemotaxis, which requires validation in larger cohorts.