Analysis of carbonic anhydrase IX and hypoxia driven metabolic adaptation relevance for tumor cell survival and antitumor immune response in lung cancer

MARIEL FUSCO; MARCO AURELIO DIAZ GUTIERREZ; FLAVIA PICCIONI; PAULA ROSELLO; MANGLIO RIZZO; MARIANA MALVICINI

Congreso; Reunion Anual de Biociencias 2022; 2022

Warburg glycolysis allows cancer cells to consume glucose under hypoxia and increase lactic acid, glutamine, and CO2 production, resulting in acidification of the tumor microenvironment. Tumor cells regulates the pH through the modulation of extracellular carbonic anhydrases (CA) such as CAIX and exchange H+ from CAIX activity releasing lactate, which reduces antitumor T cells function. Hypoxia also induces tumor-associated macrophages infiltration and stimulates the immune checkpoint Programmed Death-Ligand 1 (PD-L1). We aim to evaluate the relevance of hypoxia-associated factors and immune markers in lung cancer patients. Since we have reported that coumarin 4-methylumbelliferone (4Mu) modifies tumor HIF1 levels, and are able to inhibit CAIX, we tested the effect of 4Mu in Lewis Lung Carcinoma cells (LLC). First, we analyzed TCGA data of patients with adenocarcinoma (LUAD) and squamous cancer (LUSC), subtypes of non-small cell lung carcinoma (NSCLC). We found that HIF1a, CAIX and GLUT1 are differentially expressed in both tumors (p