biostudies-literatureLiu JNCI NIH HHSeadx8134https://www.ebi.ac.uk/biostudies/studies/S-EPMC12422196biostudies-literatureUnknown11(37)PTDSS1 (phosphatidylserine synthase 1) encodes an enzyme that facilitates production of phosphatidylserine (PS), which mediates a global immunosuppressive signal. Here, based on in vivo CRISPR screen, we identified PTDSS1 as a target to improve anti-PD-1 therapy. Depletion of Ptdss1 in tumor cells increased expression of interferon-γ (IFN-γ)-regulated genes, including B2m, Cxcl9, Cxcl10, and Stat1, even in the absence of IFN-γ stimulation in vitro. Loss of Ptdss1 in tumor cells also led to increased expression of MHC-I, enhanced cytotoxicity of CD8+ T cells, and increased frequency of an iNOS+ myeloid subset. A gene signature derived from the iNOS+ myeloid cell subset correlated with clinical benefit in patieScience advancesLoss of PTDSS1 in tumor cells improves immunogenicity and response to anti-PD-1 therapy.PMC12422196P30 CA016672Nagarajan AGoswami SLiu JHerbrich SXiong LSharma PAnandhan SBasu SChen YGuan BfalseLoss of PTDSS1 in tumor cells improves immunogenicity and response to anti-PD-1 therapy.PTDSS1 (phosphatidylserine synthase 1) encodes an enzyme that facilitates production of phosphatidylserine (PS), which mediates a global immunosuppressive signal. Here, based on in vivo CRISPR screen, we identified PTDSS1 as a target to improve anti-PD-1 therapy. Depletion of Ptdss1 in tumor cells increased expression of interferon-γ (IFN-γ)-regulated genes, including B2m, Cxcl9, Cxcl10, and Stat1, even in the absence of IFN-γ stimulation in vitro. Loss of Ptdss1 in tumor cells also led to increased expression of MHC-I, enhanced cytotoxicity of CD8+ T cells, and increased frequency of an iNOS+ myeloid subset. A gene signature derived from the iNOS+ myeloid cell subset correlated with clinical benefit in patie2025-01-01T00:00:00Z2025 Sep2026-06-02T20:21:55.043Z2026-04-20T03:10:07.819ZS-EPMC124221964092927010.1126/sciadv.adx8134