Selenium-Binding Protein 1 Deficiency Inhibits the Antitumor Immunity of Dendritic Cells

Selenium-binding protein 1 (SELENBP1) correlates positively with the prognosis of patients with colitis and colon cancer. SELENBP1-deficient dendritic cells (DCs) promote regulatory T cell differentiation and exert direct immunomodulatory functions. This study aimed to investigate whether SELENBP1-deficient DCs mediate antitumor immune function by affecting CD8⁺ T cell activation or exhaustion.

Our findings revealed that SELENBP1 deficiency in mice accelerates colon cancer progression, characterized by reduced numbers of activated DCs and cytotoxic CD8⁺ T cells, increased intratumoral exhaustion-related factors, and impaired CD8⁺ T cell tumor-killing capacity. Adoptive-transfer experiments showed that SELENBP1 deficiency impairs DC antitumor activity, which may be associated with decreased intratumoral DCs, reduced cytotoxic CD8⁺ T cells, and increased dysfunctional T cell phenotypes. Moreover, in vitro cell experiments showed that the phosphatidylinositol 3-kinase/protein kinase B and hypoxia-inducible factor-1-alpha pathways are involved in DC migration as well as DC-mediated phenotypic dysfunction of CD8⁺ T cells. In addition, SELENBP1 expression in conventional DCs correlated positively with cytotoxic CD8⁺ T cells.

This study is the first to investigate the antitumor immune function of SELENBP1 in DCs.

In vitro experiments showed that SELENBP1 deficiency impairs DC migration and maturation, resulting in decreased cytotoxic CD8⁺ T cells and increased dysfunctional T cell phenotypes. This phenomenon may underlie the accelerated colon tumor progression observed upon global SELENBP1 ablation or adoptive transfer of SELENBP1-deficient DCs. In brief, SELENBP1 deficiency impairs DC-mediated antitumor immune function. Antioxid. Redox Signal. 00, 000-000.