CEACAM1 is a direct SOX10 target and inhibits melanoma immune infiltration and stemness
John Abou‐Hamad, Jonathan J. Hodgins, Christiano Tanese de Souza, Brennan Garland, Cédrik Labrèche, Marie Marotel, Cameron Gibson, Samuel Delisle, Julia Pascoal, Rebecca C. Auer, Michele Ardolino, Luc A. Sabourin
Abstract
SOX10 is a key regulator of melanoma progression and promotes a melanocytic/differentiated state. Here we identified melanoma cell lines lacking SOX10 expression which retain their in vivo growth capabilities. More importantly, we find that SOX10 can regulate T-cell infiltration in melanoma while also decreasing common cancer stem cell (CSC) properties. We show that SOX10 regulates CEACAM1, a surface protein with immunomodulatory properties. SOX10 directly binds to a distal CEACAM1 promoter region approximately 3-4kbps from the CEACAM1 transcriptional start site. Furthermore, we show that a SOX10-CEACAM1 axis can suppress CD8 + T-cell infiltration as well as reduce CSC pool within tumors, leading to reduced tumor growth. Overall, these results identify SOX10 as a direct regulator of CEACAM1, and uncover both a pro- and anti-tumorigenic roles for SOX10 in melanoma.