Susceptibility of autologous target cells to lysis by lymphokine-activated effectors from interferon-α-treated chronic myelogenous leukaemia patients

Pawelec, Graham; Ehninger, Gerhard; Schmidt, Helmuth; Müller, Claudia; Bühring, Hans‐Jörg; Reutter, Markus; Busch, Friedrich W.

doi:10.1007/bf01771452

“…123,124,126 Second, IL3 and GM-CSF can increase the susceptibility of myeloid leukemia cells to both LAK cell lysis and Fas-induced apoptosis. 123,125,127 Taken together, these observations are consistent with the hypothesis that Fas/FasL interactions are important for non-HLA-restricted LAK cell cytotoxicity against myeloid leukemia cells.…”

supporting

confidence: 82%

“…Fas expression in AML blasts varies between patients as well as within the same blast population, [120][121][122][123][124][125][126][127] and this variability may be an explanation for the relatively large range of reported frequencies in AML patients with Fas + blasts. In one study only a minority (30%) of patients was judged to have Fas + blasts, 120 whereas in another study 80% of patients were positive.…”

mentioning

confidence: 99%

Acute myelogenous leukemia blasts as accessory cells during T lymphocyte activation: possible implications for future therapeutic strategies

Bruserud

¹

1999

View full text Add to dashboard Cite

Both clinical and experimental evidence indicate that T lymphocytes can mediate antileukemic effects in acute myelogenous leukemia (AML). These antileukemic effects can be either nonspecific cytotoxicity (killer cell activity) or reactivity against leukemia-specific antigenic peptides presented by self-HLA molecules. The antigen-specific T cell activation requires recognition of specific peptides together with costimulatory signalling. For most patients the AML blasts express both HLA class I and class II molecules for antigenic presentation, but patients are heterogeneous with regard to: (1) expression of costimulatory binding molecules; (2) expression of receptors/counterreceptors involved in induction of apoptosis; (3) constitutive release of immunomodulatory soluble mediators. This heterogeneity suggests that the ability of AML blasts to initiate an antileukemic T cell response will differ between individual patients. Thus, clinical approaches for immunotherapy in AML have to overcome three major problems. First, the therapy should reduce the patient heterogeneity so that therapeutic effects become more predictable; or alternatively one should define patient subsets which are likely to benefit from immunotherapy. Second, immunotherapy should enhance antileukemic T cell reactivity or blast susceptibility to immune attacks. Third, the therapeutic procedures must be safe and suitable for routine use. All three problems probably have to be solved before immunotherapy can become a routine treatment.

show abstract

“…Fas expression in AML blasts varies between patients as well as within the same blast population, [120][121][122][123][124][125][126][127] and this variability may be an explanation for the relatively large range of reported frequencies in AML patients with Fas + blasts. In one study only a minority (30%) of patients was judged to have Fas + blasts, 120 whereas in another study 80% of patients were positive.…”

Section: The Possible Role Of Fas/fas Ligand In Immunosuppression Indmentioning

confidence: 99%

True

1999

View full text Add to dashboard Cite

Both clinical and experimental evidence indicate that T lymphocytes can mediate antileukemic effects in acute myelogenous leukemia (AML). These antileukemic effects can be either nonspecific cytotoxicity (killer cell activity) or reactivity against leukemia-specific antigenic peptides presented by self-HLA molecules. The antigen-specific T cell activation requires recognition of specific peptides together with costimulatory signalling. For most patients the AML blasts express both HLA class I and class II molecules for antigenic presentation, but patients are heterogeneous with regard to: (1) expression of costimulatory binding molecules; (2) expression of receptors/counterreceptors involved in induction of apoptosis; (3) constitutive release of immunomodulatory soluble mediators. This heterogeneity suggests that the ability of AML blasts to initiate an antileukemic T cell response will differ between individual patients. Thus, clinical approaches for immunotherapy in AML have to overcome three major problems. First, the therapy should reduce the patient heterogeneity so that therapeutic effects become more predictable; or alternatively one should define patient subsets which are likely to benefit from immunotherapy. Second, immunotherapy should enhance antileukemic T cell reactivity or blast susceptibility to immune attacks. Third, the therapeutic procedures must be safe and suitable for routine use. All three problems probably have to be solved before immunotherapy can become a routine treatment.

show abstract