Programmed cell death regulation: basic mechanisms and therapeutic opportunities

Abstract

The molecular mechanisms responsible for induction or inhibition of apoptosis signal transduction have been intensively investigated during the past few years. Information gained from mechanistic studies and from structural analysis of apoptosis regulatory proteins has provided considerable insight into the pathways that determine whether a cell will live or die. Many of these advances were recently presented at the American

CD20 antibody (C2B8)-induced apoptosis of lymphoma cells promotes phagocytosis by dendritic cells and cross-priming of CD8+ cytotoxic T cells

“…1,[9][10][11][12] In addition to these indirect cytotoxic effects, cross-linking of CD20 with C2B8 further induces growth inhibiting and apoptotic signals in lymphoma cell lines. [13][14][15][16][17][18][19] Our results presented in this study also clearly demonstrate that treatment of the Burkitt lymphoma cell Daudi with mAb C2B8 triggered pronounced apoptotic cell death within hours in the absence of immune effector cells or complement (Figure 2). The combined action of these cell damaging mechanisms triggered by mAb C2B8 in vitro may explain the rapid depletion of normal and neoplastic B cells after C2B8 infusion found in B-NHL patients during the initial response.…”

“…[17][18][19][20][21][22][23][24][25][26][27] We therefore wondered whether mAb C2B8-treated lymphoma cells would also be recognized and ingested by DC.…”

“…1,[9][10][11][12] Yet it is more and more believed that signalling mechanisms induced by mAb C2B8 leading to apoptosis are potentially more important, since crosslinking of surface CD20 molecules with mAb C2B8 induces growth arrest and apoptosis in B cells. [13][14][15][16][17][18][19] Correspondence Recent studies have clearly shown that dendritic cells (DC) can ingest apoptotic or necrotic cells and present peptides thereof on MHC class II but also on MHC class I molecules. [20][21][22][23][24][25][26][27][28][29][30][31][32][33] The immunological consequences of such a cross-presentation event are currently hotly debated.…”

CD5-induced apoptosis of B cells in some patients with chronic lymphocytic leukemia

“…Thus, improvement of apoptosis through immmunotherapy would be of considerable value in the management of B-CLL. 4,5 Indeed, not only are the tumor cells in these patients resistant to apoptosis, 6 but defects in their programmed cell death (PCD) contribute to the failure to attain complete remission. 7 In sharp contrast to that observed in vivo, leukemic B cells undergo rapid PCD in culture, 8 and this has been profitable for studies on B-CLL apoptosis.…”

Suppression of apoptosis: role in cell growth and neoplasia

“…1 Apoptosis refers to both the initiation and execution of the events whereby a cell commits suicide and it is distinct from other forms of cell death. 2,3 Two examples of non-apoptotic cell death are: (1) necrosis -cells die from external insults such as oxygen deprivation or exposure to cytotoxic chemical agents; 4,5 (2) senescence -cells expire when they reach the end of their replicative lifetime. 6 Apoptosis is marked by an orderly series of hallmark biochemical and morphological events including cell shrinkage, mitochondrial breakdown and nuclear DNA fragmentation.…”