Abstract 3438: The CD24-SEC14L2 drives the neoplastic progression of oral squamous cell carcinoma

Abstract Immune stimulation or escape are critical factors determining the survival of malignancies, including oral squamous cell carcinoma (OSCC) and head and neck SCC (HNSCC). CD24 is a glycoprotein anchoring on cell membranes, modulating macrophages' immune responses and tumor stemness. However, its roles in the neoplastic progression are still controversial. As the inhibition of multiple oncogenic miRNAs downregulates CD24 expression, but not other immune checkpoint molecules, in murine OSCC cell lines, the functional roles of CD24 are investigated using a knockdown approach and the stable CD24 tet-off expression cell subclones. CD24 expression modulates the increase of migration and invasion and the upregulation of phosphatidylcholine/phosphatidylinositol transfer protein SEC14 Like 2 (SEC14L2) expression. CD24 expression enriches the orthotopic growth of syngeneic tumor grafts. This is accompanied by the slight change in the myeloid lineage of immune cell infiltration within tumors and the mild disruption of cell profile in recipient mice's neck lymph node and spleen. The shutdown of CD24 with doxycycline treatment drastically suppresses the growth of CD24 tet-off tumors. Concordance in CD24 and SEC14L2 expression is noted in murine tumors. SEC14L2 is upregulated in TCGA-HNSCC tumors and our OSCC tumors. High SEC14L2 expression defines the decreased B cells and myeloid cell population. The integrative analysis of combined TCGA-HNSCC and our OSCC cohort using random effect mode illustrates SEC14L2 as an unfavorable survival predictor of tumors. The oncogenic potential of the CD24-SEC14L2 axis being elucidated in this study may signify the therapeutic efficacy of CD24 targeting for oral cancer. Citation Format: Shi-Rou Chang, Chung-Hsien Chou, Kuo-Wei Chang, Shu-Chun Lin. The CD24-SEC14L2 drives the neoplastic progression of oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3438.