Abstract 999P
Background
Endemic form of nasopharyngeal carcinoma (NPC) is an EBV-associated head and neck cancer that is highly inflammatory in nature. Most patients present with locoregionally advanced disease which is treated with radiotherapy (RT) with or without chemotherapy. Studies show that plasma EBV DNA level is a prognostic factor that may predict the risk for recurrence. In this study, we have elucidated pre-treatment as well as serial changes of immune markers related to CD8+ T-cell subsets in the blood of NPC patients undergoing RT and investigated whether these changes are associated with plasma clearance of EBV DNA during RT.
Methods
We have collected peripheral blood mononuclear cells (PBMCs) of 24 NPC patients from Hong Kong treated with RT and stained PBMC with multiplex flow cytometry to assess the frequencies of T-cell subsets for T-cell differentiation, co-signalling and chemotaxis. We have analyzed the T-cell profile of these patients at baseline, during RT and post RT timepoints, and correlated these profiles to risk for recurrence.
Results
Patients with clearance versus non-clearance of post-RT EBV DNA (undetectable vs detectable EBV copies post RT) were compared, and patients who cleared EBV DNA demonstrated a lower frequency of PD1+ CD8 +T-cells, yet a higher frequency of CCR5+ expressing CD8+ T-cells during RT. The higher frequency of PD1+ CD8+ T-cells was accompanied by an enhanced T-cell differentiation status. Notably, with treatment, patients with EBV DNA clearance exclusively showed increased frequencies of CCR5+ CD8+T-cells and OX40+ CD8+ T-cells.
Conclusions
Taken together, NPC patients harbor peripheral CD8 T-cells with an antigen-experienced phenotype. In addition, these NPC patients show a lower frequency of CD8+ T-cells expressing chemo-attractant receptors, possibly halting recruitment of sufficient CD8+T-cells to the tumor site. Our outcomes, once validated, may facilitate stratification and immune monitoring of NPC patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Erasmus Medical Center, Rotterdam.
Funding
Erasmus MC Cancer Institute.
Disclosure
R. Debets: Financial Interests, Institutional, Research Grant: Merk; Financial Interests, Personal, Other, Travel expenses: Genticel; Financial Interests, Institutional, Other, consultancy fees: Bluebird Bio. All other authors have declared no conflicts of interest.