T cell homing to nasopharyngeal carcinoma

Undifferentiated nasopharyngeal carcinoma (NPC) is a very good candidate disease for treatment with adoptive T cell transfer. Uniformly Epstein-Barr virus (EBV)+, these tumours reportedly have functional antigen processing and presentation machinery and express viral proteins that contain known cytolytic T cell target epitopes. This raises the possibility that boosting relevant EBV-specific T cell immunity in NPC patients might defeat the tumour. The persistent nature of EBV infection may also encourage the long-term survival of therapeutically administered virus-specific cells. However, efficient delivery of tumour-specific T cells from the circulation to solid tumour tissue is a clear requirement for effective cellular therapy, yet the mechanisms by which T cells gain entry to NPC tumours have not yet been determined. The malignant cells of NPC are usually associated with a substantial lymphoid infiltrate mainly consisting of T cells. Using unmanipulated diagnostic biopsy samples, we have characterised chemokine receptor expression (CR) on tumour-infiltrating T cells, and established whether specific chemokine ligands are detectable at the NPC tumour site. We found that functional CXCR6 and CCR5 were expressed on tumour infiltrating T cells, consistent with the presence of specific ligands for these receptors at the tumour site. Furthermore, our data suggests that effector and regulatory cells may use shared homing mechanisms to gain entry to NPC tumours

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 tumo