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Thomas K Hoffmann

Publications and source records attributed to Thomas K Hoffmann.

20 records · Page 2Linked to original sources
PubMed2002

Alterations in the frequency of dendritic cell subsets in the peripheral circulation of patients with squamous cell carcinomas of the head and neck.

Patients with advanced squamous cell carcinomas of the head and neck (SCCHN) are frequently immunocompromised. Dendritic cells (DCs) are potent antigen-presenting cells that play a role in antitumor immune responses. Using multicolor flow cytometry, the percentages of lineage-negative (LIN(-)) and DR(+) DC precursors, as well as their LIN(-)DR(+)CD11c(+) (myeloid) and LIN(-)DR(+)CD123(+) (lymphoid) subsets, were determined in the peripheral blood of 36 patients with SCCHN before surgery. Peripheral blood mononuclear cells of 28 age- and sex-matched healthy individuals were used as controls. The proportions of LIN(-)DR(+) cells were found to be comparable in the circulation of patients and controls. However, the relative level of DR expression in LIN(-)DR(+) DC was lower in patients than in controls, suggesting a difference in the maturity of DC. The relative proportion of LIN(-)DR(+)CD123(+) cells in the LIN(-)DR(+) subset of DC did not differ significantly in patients compared with normal individuals. However, the percentage of myeloid-derived LIN(-)DR(+)CD11c(+) DCs was significantly lower (P < 0.002) in SCCHN patients than in controls. Of the 13 patients who were restudied 6 weeks after surgery, 9 showed an increase of the myeloid-derived LIN(-)DR(+)CD11c(+) DC subset postoperatively. This observation suggests that deficiency in the myeloid-derived DC precursors in patients with SCCHN is related to the presence of tumor and is reversible. An overall decrease in the myeloid-derived subset of DC could contribute to the failure of SCCHN patients to develop effective antitumor immune responses.

Adult↗
PubMed2002

Spontaneous apoptosis of circulating T lymphocytes in patients with head and neck cancer and its clinical importance.

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.

Adult↗