Interferon-gamma secretion and perforin expression are impaired in CD8+ T lymphocytes from patients with undifferentiated carcinoma of nasopharyngeal type.
An efficent antitumor and antiviral cellular immune response requires optimal interferon-gamma (IFN-gamma) 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-gamma 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-gamma production may constitute important mechanisms for immune escape by the tumor and for impaired control of EBV replication.
Zanussi
Stefania
S
Department of Microbiology, Immunology and Virology, Centro di Riferimento Oncologico, IRCCS, Via Pedemontana 12, 33081 Aviano, Italy.
Vaccher
Emanuela
E
Caffau
Cristina
C
Pratesi
Chiara
C
Crepaldi
Cinzia
C
Bortolin
Maria Teresa
MT
Tedeschi
Rosamaria
R
Politi
Doriano
D
Barzan
Luigi
L
Tirelli
Umberto
U
De Paoli
Paolo
P
D000328:Adult; D000368:Aged; D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002277:Carcinoma / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000821:virology; D004279:DNA, Viral / Q000097:blood; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000821:virology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000378:metabolism; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D019139:Tumor Escape / Q000502:physiology*; D014766:Viremia / Q000821:virology
D004279:DNA, Viral; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D007371:Interferon-gamma