Expression of pro-and antiapoptotic proteins in circulating CD8+ T cells of patients with squamous cell carcinoma of the head and neck

JW Kim, T Tsukishiro, JT Johnson, TL Whiteside - Clinical cancer research, 2004 - AACR
JW Kim, T Tsukishiro, JT Johnson, TL Whiteside
Clinical cancer research, 2004AACR
Objective: Apoptosis of T lymphocytes in the circulation of patients with squamous cell
carcinoma of the head and neck (SCCHN) was shown to target effector CD8+ rather than
CD4+ T cells. This study evaluates the contribution of pro-and antiapoptotic components of
the mitochondria-dependent pathway to apoptosis of circulating CD8+ T cells in these
patients. Experimental Design: Blood samples were obtained from 77 patients with SCCHN
and 51 normal control (s)(NC). Percentages of CD8+ Annexin V+ (ANX+) and CD8+ CD95+ …
Abstract
Objective: Apoptosis of T lymphocytes in the circulation of patients with squamous cell carcinoma of the head and neck (SCCHN) was shown to target effector CD8+ rather than CD4+ T cells. This study evaluates the contribution of pro- and antiapoptotic components of the mitochondria-dependent pathway to apoptosis of circulating CD8+ T cells in these patients.
Experimental Design: Blood samples were obtained from 77 patients with SCCHN and 51 normal control(s) (NC). Percentages of CD8+Annexin V+ (ANX+) and CD8+CD95+ cells, changes in mitochondrial membrane potential and levels of expression of Bcl-2, Bcl-XL, and Bax in CD8+ T lymphocytes were measured by quantitative flow cytometry.
Results: Elevated percentages (P < 0.001) of early apo-ptotic (CD8+ANX+ CD95+) T cells in the circulation distinguish SCCHN patients from NCs but not patients with no evidence of disease (NED) from those with active disease (AD). Circulating CD8+ but not CD4+ T cells in patients were found to contain higher levels of proapoptotic Bax and antiapoptotic Bcl-XL (P < 0.01) than NC cells. The Bax/Bcl-2 ratio was elevated in CD8+ T cells of patients relative to NCs (P < 0.01), and it correlated with the percentage of ANX+CD8+ T cells (P = 0.007). The Bax/Bcl-XL ratio discriminated AD from NED patients.
Conclusion: Apoptosis of circulating CD8+T cells is found in SCCHN patients with AD or NED. Up-regulated Bax and Bcl-XL expression, the elevated Bax/Bcl-2 ratio and its association with ANX binding implicate the mitochondrial pathway in death of CD8+ T cells of patients with SCCHN. Understanding of molecular mechanisms of T-cell death and survival is essential for the development of more effective biotherapies for SCCHN.
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