biostudies-literatureSun JChongqing Graduate Tutor Team Construction Project, Chongqing Education Commission FoundationChongqing Medical Scientific Research Project/Joint Project of Chongqing Health Commission and Science and Technology BureauNational Natural Science Foundation of ChinaNature Science Foundation of CHongqingNational Natural Science Foundation of China (NSFC)CQMU Program for Youth Innovation in Future Medicine400-416https://www.ebi.ac.uk/biostudies/studies/S-EPMC11876963biostudies-literatureUnknown13(3)The limited infiltration of CD8+ T cells in tumors hampers the effectiveness of T cell-based immunotherapy, yet the mechanisms that limit tumor infiltration by CD8+ T cells remain unclear. Through bulk RNA sequencing of human tumors, we identified a strong correlation between WNT7A expression and reduced CD8+ T-cell infiltration. Further investigation demonstrated that inhibiting WNT7A substantially enhanced MHC-I expression on tumor cells. Mechanistically, WNT7A inhibition inactivated the Wnt/β-catenin signaling pathway and thus resulted in reduced physical interaction between β-catenin and p65 in the cytoplasm, which increased the nuclear translocation of p65 and activated the NF-κB pathway, ultimately promoting the transcription of genes encoding MHC-I molecules. We found that our lead Cancer immunology researchBlocking WNT7A Enhances MHC-I Antigen Presentation and Enhances the Effectiveness of Immune Checkpoint Blockade Therapy.PMC11876963W0094cstc2021jcyj-msxmX0015 and CSTB2022NSCQ-MSX0783NO.2021MSXM033 and 2023QNXM0398217316681472475 and 822732828237288682103414cqmudstd202216Yi ZFang HLi HHuang JSong DLi QYang DWei YRen GWang PDu HChen YSun JWu YfalseBlocking WNT7A Enhances MHC-I Antigen Presentation and Enhances the Effectiveness of Immune Checkpoint Blockade Therapy.The limited infiltration of CD8+ T cells in tumors hampers the effectiveness of T cell-based immunotherapy, yet the mechanisms that limit tumor infiltration by CD8+ T cells remain unclear. Through bulk RNA sequencing of human tumors, we identified a strong correlation between WNT7A expression and reduced CD8+ T-cell infiltration. Further investigation demonstrated that inhibiting WNT7A substantially enhanced MHC-I expression on tumor cells. Mechanistically, WNT7A inhibition inactivated the Wnt/β-catenin signaling pathway and thus resulted in reduced physical interaction between β-catenin and p65 in the cytoplasm, which increased the nuclear translocation of p65 and activated the NF-κB pathway, ultimately promoting the transcription of genes encoding MHC-I molecules. We found that our lead 2025-01-01T00:00:00Z2025 Mar2026-06-01T23:11:25.028Z2025-04-04T02:11:07.522ZS-EPMC118769633960246210.1158/2326-6066.CIR-24-0484