CXCR6 and CCR5 localize T lymphocyte subsets in nasopharyngeal carcinoma.
The substantial T lymphocyte infiltrate found in cases of nasopharyngeal carcinoma (NPC) has been implicated in the promotion of both tumor growth and immune escape. Conversely, because malignant NPC cells harbor the Epstein-Barr virus, this tumor is a candidate for virus-specific T cell-based therapies. Preventing the accumulation of tumor-promoting T cells or enhancing the recruitment of tumor-specific cytotoxic T cells offers therapeutic potential. However, the mechanisms involved in T cell recruitment to this tumor are poorly understood. Comparing memory T cell subsets that have naturally infiltrated NPC tissue with their counterparts from matched blood revealed enrichment of CD8(+), CD4(+), and regulatory T cells expressing the chemokine receptor CXCR6 in tumor tissue. CD8(+) and (nonregulatory) CD4(+) T cells also were more frequently CCR5(+) in tumor than in blood. Ex vivo studies demonstrated that both receptors were functional. CXCL16 and CCL4, unique chemokine ligands for CXCR6 and CCR5, respectively, were expressed by the malignant cells in tumor tissue from the majority of NPC cases, as was another CCR5 ligand, CCL5. The strongest expression of CXCL16 was found on tumor-infiltrating cells. CCL4 was detected on the tumor vasculature in a majority of cases. These findings suggest that CXCR6 and CCR5 play important roles in T cell recruitment and/or retention in NPC and have implications for the pathogenesis and treatment of this tumor.
School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom.
Greg
G
Parsonage
School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom.
Lee Richard
LR
Machado
Department of Anatomical and Cellular Pathology, Sir YK Pao Centre for Cancer, Chinese University of Hong Kong, Hong Kong.
Jan Wai-Ying
JW
Hui
School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom.
Andrew
A
McLarnon
School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom.
Tilo
T
Schmaler
School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom.
Meenarani
M
Balasothy
Department of Anatomical and Cellular Pathology, Sir YK Pao Centre for Cancer, Chinese University of Hong Kong, Hong Kong.
Ka-Fai
KF
To
Department of Otorhinolaryngology, Head and Neck Surgery, Chinese University of Hong Kong, Hong Kong.
Alexander C
AC
Vlantis
Department of Otorhinolaryngology, Head and Neck Surgery, Chinese University of Hong Kong, Hong Kong.
Charles A
CA
van Hasselt
Department of Anatomical and Cellular Pathology, Sir YK Pao Centre for Cancer, Chinese University of Hong Kong, Hong Kong.
Kwok-Wai
KW
Lo
Department of Clinical Oncology, Sir YK Pao Centre for Cancer, Chinese University of Hong Kong, Hong Kong.
Wai-Lap
WL
Wong
Department of Clinical Oncology, Sir YK Pao Centre for Cancer, Chinese University of Hong Kong, Hong Kong.
Edwin Pun
EP
Hui
Department of Clinical Oncology, Sir YK Pao Centre for Cancer, Chinese University of Hong Kong, Hong Kong.
Anthony Tak Cheung
ATC
Chan
School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom. Electronic address: s.p.lee@bham.ac.uk.
Steven P
SP
Lee
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002277:Carcinoma; D045744:Cell Line, Tumor; D006801:Humans; D007156:Immunologic Memory / Q000502:physiology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000276:immunology*; D019713:Receptors, CCR5 / Q000378:metabolism* / Q000502:physiology; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000378:metabolism* / Q000502:physiology; D011991:Receptors, Virus / Q000378:metabolism* / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
C106330:CXCR6 protein, human; D019713:Receptors, CCR5; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D011991:Receptors, Virus