title: Spontaneous apoptosis of circulating T lymphocytes in patients with head and neck cancer and its clinical importance.
abstract: Spontaneous apoptosis was observed in a proportion of peripheral blood mononuclear cells obtained from patients with head and neck cancer (HNC) but not from normal healthy donors (T. Saito et al., Clin. Cancer Res., 5: 1263-1273, 1999). To further investigate this phenomenon, peripheral blood mononuclear cells were obtained from patients with HNC or normal controls (NCs) and evaluated for expression of apoptosis markers (annexin V binding and caspase-3 activation), T-cell receptor-associated zeta chain, and the death receptor Fas (APO-1, CD95) in CD3(+) T cells by multicolor flow cytometry. Soluble Fas ligand (sFasL) in the sera of these individuals was quantitated by ELISA. In patients with HNC, 74 +/- 15% (mean +/- SD) of CD3(+) T cells were Fas(+) compared with 52 +/- 13% in NCs (P < 0.0001). Furthermore, 29 +/- 16% of the Fas(+) CD3(+) T cells bound annexin V in patients and only 14% +/- 7% of the Fas(+) CD3(+) T cells bound annexin V in NCs (P < 0.0001). In patients, Fas(+) CD3(+) cells preferentially underwent apoptosis and showed a loss of zeta chain expression. Significantly greater proportions of CD8(+) T cells than CD4(+) T cells were apoptotic (P < 0.0002), which indicates that CD8(+) T cells were especially sensitive to apoptosis. Serum levels of sFasL were lower in HNC patients with active disease than in NCs or in patients with no evident disease (P < 0.0183). This suggested utilization of sFasL produced in vivo and activation of the Fas/Fas ligand (FasL) pathway in Fas(+) T cells. Proportions of apoptotic T cells were higher in HNC patients than in NCs (P < 0.0001), and a subset of HNC patients with active disease had the highest proportions of circulating Fas(+) annexin V(+) T lymphocytes. The data indicate that the Fas/FasL pathway is involved in spontaneous apoptosis of circulating Fas(+) T lymphocytes in cancer patients. Fas/FasL interactions might lead to excessive turnover of T cells in the circulation and, consequently, to reduced immune competence in patients with HNC.
authors.affiliation: University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213-2582, USA.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Hoffmann
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Dworacki
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsukihiro
authors.forename: Norbert
authors.initials: N
authors.lastname: Meidenbauer
authors.forename: William
authors.initials: W
authors.lastname: Gooding
authors.forename: Jonas T
authors.initials: JT
authors.lastname: Johnson
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Whiteside
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000473:pathology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004396:Coloring Agents / Q000494:pharmacology; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000097:blood* / Q000473:pathology*; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism
chemical_list: D017304:Annexin A5; D017252:CD3 Complex; D004396:Coloring Agents; D019014:fas Receptor; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases