Insights Regarding the Role of Inflammasomes in Leukemia: What Do We Know?

Figure 1

Inflammation-based model of leukemia development. A genetic alteration produced in the uterus would be responsible for the creation of a leukemic clone. After birth, due to the low stimulation of the immune system, a dysregulated immune response to common pathogens would occur, culminating in an exacerbated inflammatory response. Inflammasomes stand out as important mediators of inflammation in innate immunity through the recognition of PAMPs and DAMPs, which leads to the maturation and secretion of proinflammatory cytokines IL-1β and IL-18, and through the cell death process via pyroptosis. The cytokine IL-1β has pleiotropic functions in the tumor and can be secreted by both leukemic and stromal cells. It is responsible for the recruitment of myeloid-derived suppressor cells (MDSCs) that secrete IL-10 and TGF-β and induce the differentiation of TCD4+ lymphocytes into Tregs, thus promoting immunosuppression. In addition, binding to the IL1R receptor promotes a positive loop of autocrine/paracrine secretion of this cytokine in leukemic cells and, through activation of the NF-κB pathway, this leads to the transcription of other inflammatory mediators, such as TNF-α, IL-10, and IL-12, that are secreted into the TME. Together, these mechanisms are responsible for inducing mitochondrial dysfunction, oxidative stress, and persistent DNA damage, which lead to the acquisition of secondary genetic alterations that contribute to the development of leukemia. Abbreviations: DAMPs, damage-associated molecular patterns; DNA, deoxyribonucleic acid; IL-10, interleukin-10; IL-12, interleukin-12; IL-18, interleukin-18; IL-1β, interleukin-1β; PAMPs, pathogen-associated molecular pattern molecules (PAMPs); TCD4+, lymphocyte CD34+; TGFβ, transforming growth factor β; TME, tumor microenvironment; TNF-α, tumor necrosis factor-α; Tregs, regulatory T cells; ?, Influence on the known.