Interleukin-10 expression and cytotoxic-T-cell response in Epstein-Barr-virus-associated nasopharyngeal carcinoma

Abstract

Interleukin-10 (IL-10) is an inhibitory cytokine produced by various cell types. It exhibits strong sequence homology to BCRF-1 (viral IL-10, vIL-10), an open reading frame in the Epstein-Barr-virus (EBV) genome. Using in situ hybridization (ISH), polymerase chain reaction (PCR) and immunohistochemistry, we checked 41 cases of nasopharyngeal carcinoma (NPC), to study the presence of EBV in the tumor cells, as well as to clarify the relationship between IL-10 expression of the tumor cells and the response of cytotoxic T cells. IL-10 expression was studied by immunohistochemistry; as a result, 29 of 41 cases expressed EBER-1 RNA of EBV by ISH. In addition, 19 of the 29 with EBV and 9 of 12 without EBV cases expressed IL-10 in the tumor cells. The number of cytotoxic T cells increased in the tumor tissue, and the increase in the intratumoral stroma was stronger than in the remaining normal epithelia. The number of cytotoxic T cells also significantly increased in the cases with EBV. On the other hand, in the IL-10-positive series, the number of cytotoxic T cells decreased significantly more than in IL-10-negative series. In view of the established inhibitory effects of IL-10, expression of IL-10 may therefore be one of the mechanisms for NPC cells as well as EBV to counter local immune defense. However, we could not conclude whether or not IL-10 expression was directly induced by EBV.

CTL Control of EBV in Nasopharyngeal Carcinoma (NPC): EBV-Specific CTL Responses in the Blood and Tumors of NPC Patients and the Antigen-Processing Function of the Tumor Cells

“…One possible mechanism for this could be through the action of cytokines such as IL-10, which is known to suppress cellular immune responses (49). IL-10 is also expressed in NPC tumors (50), yet our findings demonstrate that EBV-specific CTLs can be cultured from NPC biopsies and display Ag-specific cytolytic activity in vitro. However, we did not detect any responses to LMP2 or any other NPC-associated viral protein.…”

Increase of programmed death-1-expressing intratumoral CD8 T cells predicts a poor prognosis for nasopharyngeal carcinoma

“…Impairment of anti-tumor immune responses prevents the body from clearing residual tumor cells after radiotherapy or chemotherapy, which increases the risk of tumor recurrence after treatment. 4,5 Multiple immunosuppressive mechanisms in nasopharyngeal carcinoma have been proposed: interleukin-10, 26 transforming growth factor b1, 27 Fas ligand, 28 regulatory T cells, 29 and galectin-9. 30 As most of these mechanisms converge to inhibit effector T cells, we hypothesized that a marker summarizing the suppressive status of TILs would help identify nasopharyngeal cancer patients with a high risk of treatment failure after standard radiotherapy or chemotherapy.…”

Type 2 Cytokines Predominate in the Human CD4+T-Lymphocyte Response to Epstein-Barr Virus Nuclear Antigen 1

“…Indeed, viral and human IL-10 has been implicated in a local suppression of EBV-specific immune recognition of EBV-positive Hodgkin's lymphomas and nasopharyngeal carcinomas (19,31,44,64). In this context, it is noteworthy that many EBV-positive malignancies demonstrate a latency II pattern of EBV gene expression (49), in which latent nuclear antigen expression is restricted to EBNA1, with variable levels of the latent membrane proteins.…”