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.
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.
Authors: Lin Lin; Patricia Rayman; Paul G Pavicic; Charles Tannenbaum; Thomas Hamilton; Alberto Montero; Jennifer Ko; Brian Gastman; James Finke; Marc Ernstoff; C Marcela Diaz-Montero Journal: Cancer Immunol Immunother Date: 2018-12-14 Impact factor: 6.968
Authors: Christoph Bergmann; Laura Strauss; Eva Wieckowski; Malgorzata Czystowska; Andreas Albers; Yun Wang; Reinhard Zeidler; Stephan Lang; Theresa L Whiteside Journal: Head Neck Date: 2009-03 Impact factor: 3.147
Authors: Andreas E Albers; Carsten Schaefer; Carmen Visus; William Gooding; Albert B DeLeo; Theresa L Whiteside Journal: Head Neck Date: 2009-06 Impact factor: 3.147