Francesca Peruzzi, PhD
fperuz@lsuhsc.edu
Associate Professor
Mechanisms of innate immune dysfunction in viral infection and cancer
A) People living with HIV (PLWH) are at high risk of developing secondary illnesses including cancer. Although combined antiretroviral therapy (cART) reduces the viral load and increases the life span of these patients, it does not fully restore the full function of immune cells, sensitizing them to secondary infections and other pathologies. When exposed to environmental signals, such as β-glucan or lipopolysaccharide (LPS) endotoxins, normal monocytes will execute two types of innate programming called “trained immunity” and “tolerance” characterized by either hyper-responsiveness or hypo-responsiveness to secondary stimuli, respectively. We demonstrated that the transcription factor IKAROS plays a key role in maintaining this delicate balance between trained immunity and tolerance in monocytes. Our current project further investigates the mechanisms of IKAROS-mediated metabolic reprogramming and dysfunctional immune response.
B) While IKAROS functions as a tumor suppressor in several leukemias and lymphomas, its aberrant expression has been linked to tumor progression. In glioblastoma, tumor-associated macrophages (TAMs) exhibit elevated expression of IKAROS, which contributes to the polarization of TAMs toward an M2-like, immunosuppressive phenotype, supporting tumor progression and creating a permissive tumor microenvironment. Current work in our lab is aimed at targeting IKAROS in TAMs as a strategy to shift macrophage function toward a pro-inflammatory, anti-tumoral state.