Spontaneous ex vivo apoptosis of peripheral blood mononuclear cells in patients with head and neck cancer

Proportions of apoptotic (TUNEL+) peripheral blood mononuclear cells (PBMCs ) were measured by flow cytometry in patients with head and neck cancer and normal controls at the time of blood draws (0 time) and after 24-h incubat ion, PBMCs were incubated at 37 degrees C in medium (spontaneous apoptosis) and in the presence of CH-11 antibody (anti-Fas) or tumor necrosis factor (TNF)-alpha, both capable of inducing DNA fragmentation in activated T cell s expressing the TNF family of receptors, PBMCs obtained from the patients had significantly higher (P < 0.0001) proportion of apoptotic cells than PB MCs of controls at 0 time as well as after 24-h incubation. Ex vivo apoptos is included all subsets of PBMCs: CD3(+) T cells, CD16(+)CD56(+) natural ki ller cells, CD19(+) B cells, and CD14(+) monocytes, as determined by two-co lor flow cytometry, However, T cells represented the largest PBMC subset un dergoing apoptosis, and lymphocytes rather than monocytes were the major TU NEL+ PBMC population. Among T cells, the level of spontaneous ex vivo apopt osis was nearly as high as that of CH-11 antibody-induced or TNP-alpha-indu ced apoptosis, indicating that activated Fas(+) and TNFR1(+) T cells were p reprogrammed in vivo to die. Also, elevated levels of spontaneous apoptosis at time 0 in patients with head and neck cancer (P < 0.0001) indicated tha t a higher fraction of PBMCs was undergoing apoptosis in vivo in patients t han controls, Together, the data suggest that an increased rate of turnover of lymphocytes is associated with cancer and may be responsible for functi onal lymphocyte imbalance, even in treated patients who have no evident dis ease.