Alginate Enhances Memory Properties of Antitumor CD8⁺ T Cells by Promoting Cellular Antioxidation

Alginate, an FDA-approved natural biomaterial usually used as a therapeutic adjuvant, drug carrier, and biological scaffold, reportedly assists the immune system to activate cytotoxic T cells in antitumor assays. In this study, we investigated the direct effect of alginate on cytotoxic T cell function. By incubating sorted cytotoxic CD8⁺ T cells with alginate, we found that this material facilitated the antitumor cytotoxic activities of T cells. Alginate incubation significantly promoted memory properties of CD8⁺ T cells and elevated the proportion of CD62L⁺CD44⁺ central memory T cell (TCM), a less differentiated T cell subset with high immune activity. Mechanistically, alginate reduced reactive oxide species in CD8⁺ T cells by increasing intracellular glutathione generation, which was critical for conferring T cells with memory properties. Further, we found that guluronic acid, a constituent component (G unit) of alginate, is responsible for inducing glutathione and promoting TCM. Collectively, we reported new biological activities of alginate on scavenging reactive oxide species and regulating the function of cytotoxic T cells, which suggests that alginate and guluronic acid may be used for improving cytotoxic T cell functions in immunotherapy.