CARBONIC ANHYDRASE IX AND HYPOXIA-ASSOCIATED METABOLIC CHANGES: A FIRST APPROACH TO THE IMPACT IN TUMOR CELL SURVIVAL AND THE IMMUNE RESPONSE IN LUNG CANCER

FUSCO, MARIEL; DÍAZ GUTIERREZ, MARCO A; VICTORIA, LUCÍA; PICCIONI, FLAVIA VALERIA; ROSELLO, PAULA; ARRIOLA BENITEZ, CONSTANZA; RIZZO, MANGLIO; MALVICINI, MARIANA

San Luis

Congreso; LXXI REUNIÓN CIENTÍFICA ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI); 2023

Sociedad Argentina de Inmunología

In solid tumors such as lung cancer, tumor survival is, at least in part, sustainedby a repertoire of effects induced by pH regulation and glycolysis under low oxygentension (hypoxia). Then, cancer cells increase lactic acid, glutamine, and CO2production, resulting in acidification of the tumor microenvironment (TME). Tumorcells regulate the pH through the modulation of extracellular carbonic anhydrases(CA) such as CAIX and exchange H+ from CAIX activity releasing lactate, whichcould modify the function of immune cells. Hypoxia also induces the recruitmentof tumor-associated macrophages (TAMs, which could express CD68 or CD163),and stimulates the immune checkpoint Programmed Death-Ligand 1 (PD-L1).Previously, we analyzed the relevance of hypoxia- associated factors and immunemarkers in lung cancer patients. We found that hypoxia-inducible factor 1a (HIF1a)and CAIX are differentially expressed in adenocarcinoma (LUAD) and squamouscancer (LUSC), subtypes of non-small cell lung carcinoma (NSCLC) (p