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

AIMS: 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. RESULTS: 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. INNOVATION: This study is the first to investigate the antitumor immune function of SELENBP1 in DCs. CONCLUSION: 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.