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

FIAMA BOUCHARD; LUZ MARÍA PALACIOS; NICOLAS DHO; CINTIA ARAUJO FURLAN; FEDERICO RUIZ MORENO; BELKYS MALETTO; GABRIEL MORON; MARÍA INES CRESPO

Congreso; LXXI REUNIÓN SAI; 2023

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