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.
Original language | English |
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Article number | 1887 |
Journal | Cancers |
Volume | 15 |
Issue number | 6 |
DOIs | |
Publication status | Published - Mar 2023 |
Bibliographical note
Funding Information:This work is supported in part by an Erasmus MC-CUHK grant to advocate inter-institutional collaborations, the Kingboard Charity Foundation and the Charlie Lee Precision Immuno-oncology Program of the Chinese University of Hong Kong, Hong Kong SAR.
Funding Information:
K W Lo: research support from Viracta therapeutics, ScinnoHub Pharmaceutical Co., Ltd., Hong Kong Research Grant Council (AoE/M401/20; GRF: 14101721) and Innovation and Technology Fund (ITF: MRP/036/21X). Edwin P Hui: Grant/research/clinical trial support from Merck Sharp & Dohme; Pfizer, consultant/advisory boards: Merck Sharp & Dohme. Jacky Lam: Equity in Grail Inc. He has filed multiple patents/patent applications on the use of circulating nucleic acids for cancer diagnostics. Brigette Ma: MSD, Novartis, Viracta Therapeutics, Y-biologics, Merck, Y-Biologics, Daiichi, Taiho Pierre Fabre. Reno Debets: received research support from MSD and Bayer, personal fees from Bluebird Bio, Genticel, Sanofi, other support from Pan Cancer T outside the submitted work (all paid to the Erasmus MC Cancer Institute), as well as European patent application no’s. 21152822.9 and 21184727.2 (pending to Erasmus MC).
Publisher Copyright:
© 2023 by the authors.