DEVELOPMENT OF MURINE MODELS OF ORAL CANCER ASSOCIATED WITH TOBACCO EXPOSURE TO STUDY THE CD44 RECEPTOR RELEVANCE IN TUMOR GROWTH, PROGRESSION AND RESPONSE TO IMMUNOTHERAPY

MARIEL A. FUSCO; LUCIA VICTORIA; FLAVIA PICCIONI; MARIANA MALVICINI

Congreso; Reunión Conjunta de Sociedades de Biociencia; 2023

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, causing around 3,000 deaths annually in Argentina. The curative option is surgical resection but most patients can access it because the diagnosis is usually in advanced disease. The elucidation of the genomic alterations of HNSCC that can promote recognition by the immune system (IS) and the approaches based on the activation of the antitumor immune response (immunotherapy) became an opportunity for HNSCC, and immune checkpoint inhibitors are approved for HNSCC. Primary and acquired resistance to therapies, including immunotherapy, could be mediated by tumor-initiating cells (CSCs), which are part of the tumor microenvironment (TME) and are characterized by markers such as CD133 and CD44, a different proliferation and self-renewal, and the ability to evade IS. Lately, an increase in CD44 expression levels was described in HNSCC tumors. We induced carcinogenesis that mimics the mutational complexity of tobacco-associated HNSCC by administering the drug 1-oxide 4-nitroquinoline (4NQO) in wild-type (WT) and deficient expression of the CD44 gene (CD44KO) mice. After 22 weeks, we observed tumor lesions in both strains. While WT showed tumor growth in all mice exposed to 4NQO, CD44KO showed lesions in 50% of mice, suggesting a possible role of CD44 in tumor development. With the aim of obtaining a shorter and easier-to-follow-up model, we isolated, cultured, and establish WT or CD44KO cell lines. We phenotypically characterized lines and challenged WT or CD44KO C57 mice in the tongue or s.c with CD44+/+cells. We observed tumor growth in both models; however, tumor-bearing WTC57 mice showed a lower rate compared to CD44KO mice (p