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

Both clinical and experimental evidence indicate that T lymphocytes can med iate antileukemic effects in acute myelogenous leukemia (AML). These antile ukemic effects can be either nonspecific cytotoxicity (killer cell activity ) or reactivity against leukemia-specific antigenic peptides presented by s elf-HLA molecules. The antigen-specific T cell activation requires recognit ion of specific peptides together with costimulatory signalling. For most p atients 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 relea se 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 immunothe rapy in AML have to overcome three major problems. First, the therapy shoul d reduce the patient heterogeneity so that therapeutic effects become more predictable; or alternatively one should define patient subsets which are l ikely to benefit from immunotherapy. Second, immunotherapy should enhance a ntileukemic T cell reactivity or blast susceptibility to immune attacks. Th ird, the therapeutic procedures must be safe and suitable for routine use. All three problems probably have to be solved before immunotherapy can beco me a routine treatment.