UNVEILING THE ROLE OF LIPID METABOLISM IN ENHANCING ANTIGEN CROSS-PRESENTATION BY PERHEXILINE MALEATESTIMULATED DENDRITIC CELLS

FIAMA BOUCHARD; LUZ MARÍA PALACIOS; NICOLÁS DANIEL DHO; CINTIA ARAUJO FURLÁN; FEDERICO RUIZ MORENO; BELKYS MALETTO; GABRIEL MORÓN; MARÍA INÉS CRESPO

San Luis

Congreso; LXXI Reunión Científica Anual de la Sociedad Argentina de Inmunología SAI; 2023

Sociedad Argentina de Inmunología SAI

The immune response mediated by cytotoxic CD8+ T cells (CTLs) plays a pivotalrole in both tumor immunotherapy and defense against intracellular pathogens.Dendritic cells (DCs) have the ability to internalize and present exogenousantigens (Ag) via MHC I to activate naïve CD8+ T cells, a process termed crosspresentation. Adjuvants are necessary to robust CTL response, especially insubunit vaccines. However, due to the intricate nature of Ag cross-presentationpathways, identifying therapeutic targets that can serve as adjuvants forgenerating protective CTL responses has proven challenging. To address this,we previously performed a high throughput screening of drug libraries approvedby international agencies. The aim was to identify novel compounds andmolecular pathways capable of enhancing Ag cross-presentation in DCs. Ourapproach involved the adaptation of the B3Z presentation assay using theJAWSII DC cell line and Ovalbumin (OVA) as the soluble Ag. In this study, weelucidate the mechanisms underlying the enhancement of cross- presentationby Perhexiline Maleate (PM), one of the five active compounds identified.Notably, PM does not influence OVA internalization nor MHC I-surfaceexpression in JAWSII DCs. Moreover, incubating JAWSII DCs with PM led toincreased translocation of Ags from endosomes to the cytosol (p