Interferon-γ secretion and perforin expression are impaired in CD8⁺ T lymphocytes from patients with undifferentiated carcinoma of nasopharyngeal type

Abstract.

An efficent antitumor and antiviral cellular immune response requires optimal interferon-γ (IFN-γ) secretion and perforin expression in CD8⁺ T cells. The aim of this study was to define whether CD4⁺ and CD8⁺ T cells from patients with undifferentiated carcinoma of nasopharyngeal type (UCNT), a tumor regularly associated with the Epstein-Barr virus (EBV), have abnormal phenotype profiles, cytokine production, perforin and CD3-zeta expressions. Our data showed that CD4 and CD8 subset distribution was not grossly altered in the peripheral blood of UCNT patients, while tumor biopsies contained an increased proportion of CD8⁺ T cells. The analysis of the CD4⁺ subset showed a defect in interleukin-2 (IL-2) production and a moderate increase of IL-10 production, a situation consistent with a Th1/Th2 imbalance. We have also demonstrated that CD8⁺ lymphocytes from UCNT patients had a marked impairment of IFN-γ secretion and perforin expression. This impairment was not related to the presence of detectable EBV DNA in the plasma. In UCNT patients, the blockade of the perforin pathway and of IFN-γ production may constitute important mechanisms for immune escape by the tumor and for impaired control of EBV replication.