biostudies-literatureUnknown17(1)Liu TLymphocyte antigen-plasminogen activator urokinase receptor domain-containing protein 6B (Lypd6b) is a newly identified molecule associated with neuromodulation. However, the role of Lypd6b in regulating the tumor microenvironment and its impact on CD8⁺ T cell-mediated antitumor immunity remain unknown. Here, we observe that Lypd6b expression is increased significantly in colorectal cancer (CRC) tumor tissues compared to normal tissues. Lypd6b is mainly expressed in CD8⁺ T cells in tumor tissues. Lypd6b knockout (Lypd6b^-/-) mice are resistant to AOM/DSS-induced tumorigenesis. Furthermore, global deficiency or CD8⁺ cell deficiency of Lypd6b inhibits MC38 or CMT-93 tumor growth and promotes the infiltration of CD8⁺ T cells. MechanisticalNature communications675https://www.ebi.ac.uk/biostudies/studies/S-EPMC12820146biostudies-literatureLypd6b depletion promotes CD8<sup>+</sup> T cell-mediated anti-tumor immunity via metabolic reprogramming in colorectal cancer.PMC12820146Yao JZhang JXu DLiu QWang FChen HLiu TYan XWang JLi XLi ZChen ZCheng LZeng FfalseLypd6b depletion promotes CD8<sup>+</sup> T cell-mediated anti-tumor immunity via metabolic reprogramming in colorectal cancer.Lymphocyte antigen-plasminogen activator urokinase receptor domain-containing protein 6B (Lypd6b) is a newly identified molecule associated with neuromodulation. However, the role of Lypd6b in regulating the tumor microenvironment and its impact on CD8⁺ T cell-mediated antitumor immunity remain unknown. Here, we observe that Lypd6b expression is increased significantly in colorectal cancer (CRC) tumor tissues compared to normal tissues. Lypd6b is mainly expressed in CD8⁺ T cells in tumor tissues. Lypd6b knockout (Lypd6b^-/-) mice are resistant to AOM/DSS-induced tumorigenesis. Furthermore, global deficiency or CD8⁺ cell deficiency of Lypd6b inhibits MC38 or CMT-93 tumor growth and promotes the infiltration of CD8⁺ T cells. Mechanistical2025-01-01T00:00:00Z2025 Dec2026-06-14T05:04:55.397Z2026-06-14T03:08:42.245ZS-EPMC128201464138152410.1038/s41467-025-67344-w