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

Shweta Mahajan*, Hayri E. Balcioglu, Astrid Oostvogels, Willem A. Dik, K. C.Allen Chan, Kwok Wai Lo, Edwin P. Hui, Anna Tsang, Joanna Tong, Wai Kei Jacky Lam, Kenneth Wong, Anthony T.C. Chan, Brigette B.Y. Ma, Reno Debets

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

53 Downloads (Pure)

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 languageEnglish
Article number1887
JournalCancers
Volume15
Issue number6
DOIs
Publication statusPublished - 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.

Fingerprint

Dive into the research topics of 'Frequency of Peripheral CD8+ T Cells Expressing Chemo-Attractant Receptors CCR1, 4 and 5 Increases in NPC Patients with EBV Clearance upon Radiotherapy'. Together they form a unique fingerprint.

Cite this