RESUMEN
Acute myeloid leukemia (AML) is an aggressive hematologic cancer in adults. Some patients exhibit restricted T cell infiltration and do not respond to routine treatments. This may be prevented by enhancing adaptive immunity by stimulating innate immune cells inside the tumor microenvironment (TME). To activate the adaptive immunological reaction against tumors, type I interferons (IFNs) can promote the presentation of tumor-specific cytotoxic T lymphocyte (CTL) cell recruitment. During the activation of innate immunity, cyclic di-nucleotides (CDNs) bind to and stimulate the stimulator of interferon genes (STING), a protein localized inside the endoplasmic reticulum (ER) membrane, resulting in the expression of type I IFNs. The efficacy of STING agonists as effective stimulators of the anti-tumor response in AML is being investigated in numerous clinical studies. Therefore, the purpose of this investigation was to thoroughly review existing knowledge in this field and provide perspective into the clinical potential of STING agonists in AML.
Asunto(s)
Inmunidad Innata , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Nucleótidos Cíclicos , Inmunidad Adaptativa , Interferones , Inmunoterapia/métodos , Microambiente TumoralRESUMEN
Acute myeloid leukemia (AML) is an aggressive type of blood cancer affecting bone marrow (BM). In AML, hematopoietic precursors are arrested in the early stages of development and are defined as the presence of ≥ 20% blasts (leukemia cells) in the BM. Toll-like receptors (TLR) are major groups of pattern recognition receptors expressed by almost all innate immune cells that enable them to detect a wide range of pathogen-associated molecular patterns and damage-associated molecular patterns to prime immune responses toward adaptive immunity. Because TLRs are commonly expressed on transformed immune system cells (ranging from blasts to memory cells), they can be a potential option for developing efficient clinical alternatives in hematologic tumors. This is because several in vitro and in vivo investigations have demonstrated that TLR signaling increased the immunogenicity of AML cells, making them more vulnerable to T cell-mediated invasion. This study aimed to review the current knowledge in this field and provide some insight into the therapeutic potentials of TLRs in AML.