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

MARIEL FUSCO; DIAZ GUTIERREZ MARCO AURELIO; LUCIA VICTORIA; FLAVIA PICCIONI; PAULA ROSELLÓ; ARRIOLA BENITEZ, P. CONSTANZA; MANGLIO MIGUEL RIZZO; MARIANA MALVICINI

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

In solid tumors such as lung cancer, tumor survival is, at least in part, sustained by a repertoire of effects induced by pH regulation and glycolysis under low oxygen tension (hypoxia). Then, cancer cells increase lactic acid, glutamine, and CO2 production, resulting in acidification of the tumor microenvironment (TME). Tumor cells regulate the pH through the modulation of extracellular carbonic anhydrases (CA) such as CAIX and exchange H+ from CAIX activity releasing lactate, which could modify the function of immune cells. Hypoxia also induces the recruitment of 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 immune markers in lung cancer patients. We found that hypoxia-inducible factor 1a (HIF1a) and CAIX are differentially expressed in adenocarcinoma (LUAD) and squamous cancer (LUSC), subtypes of non-small cell lung carcinoma (NSCLC) (p