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Loss of PTDSS1 in tumor cells improves immunogenicity and response to anti-PD-1 therapy [RNA-seq]

ABSTRACT: Loss of PTDSS1 in tumor cells improves immunogenicity and response to anti-PD-1 therapy [RNA-seq]

PROVIDER: PRJNA1238825 | ENA |

REPOSITORIES: ENA

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Loss of PTDSS1 in tumor cells improves immunogenicity and response to anti-PD-1 therapy [scRNAseq]

Project description: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 IFNγ-regulated genes, including B2m, Cxcl9, Cxcl10, and Stat1, even in the absence of IFNγ stimulation in vitro. Loss of PTDSS1 in tumor cells also led to increased expression of MHC-I, which was associated with 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 patients treated with anti-PD-1 therapy. Moreover, genetic and pharmacological inhibition of PTDSS1 in different tumor models improved anti-PD-1 therapy. Together, our results provide insights on a new therapeutic strategy for overcoming immunosuppression by inhibiting PTDSS1 and provide rationale for development of a combination immunotherapy strategy comprised of PTDSS1 inhibition plus PD-1 blockade.

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Loss of PTDSS1 in tumor cells improves immunogenicity and response to anti-PD-1 therapy [AmpSeq]

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Loss of PTDSS1 in tumor cells improves immunogenicity and response to anti-PD-1 therapy [RNA-seq]

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Loss of PTDSS1 in tumor cells improves immunogenicity and response to anti-PD-1 therapy [scRNAseq]

Project description:Loss of PTDSS1 in tumor cells improves immunogenicity and response to anti-PD-1 therapy [scRNAseq]

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Loss of PTDSS1 in tumor cells improves immunogenicity and response to anti-PD-1 therapy [AmpSeq]

Project description:Loss of PTDSS1 in tumor cells improves immunogenicity and response to anti-PD-1 therapy [AmpSeq]

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PD-1-PD-L1 Axis Activation Suppresses CD8+ T Cells and Improves Nephritis.

Project description:PD-1-PD-L1 Axis Activation Suppresses CD8+ T Cells and Improves Nephritis.

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Impact of Ptdss1 knockdown in tumor cells and Mertk KO in macrophages on tumor-associated macrophage phenotype

Project description:We studied the impact of Ptdss1 knockdown in PyMT mouse mammary tumor cells and of Csf1-driven Mertk KO (macrophage-specfic) on tumor growth and the associated macrophage phenotype in an orthotopic tumor model. To gain insight into the reasons underlying tumor rejection once either Ptdss1 was deleted in tumor cells or Mertk was knocked out in macrophages, whole transcriptome profiling of FACS-sorted tumor-associated macrophages of WT or macrophage-specific Mertk KO mice receiving either control tumor cells or Ptdss1 knockdown tumor cells was performed via next generation mRNA sequencing, at least in triplicates, on a NextSeq 500 high-throughput bench top sequencer.

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Potent and selective PTDSS1 inhibitor targeting collateral lethality against cancer with PTDSS2 deletion [xeno_RNA-seq]

Project description:To decipher the underlying mechanism governing selective growth arrest in PTDSS1-inhibited PTDSS2-depleted cancer cells, we analyzed the transcriptomic changes brought about by comparing vehecle treated and DS55980254 treated PTDSS2-KO HCT116 s.c. tumors.

2022-08-31 | GSE206517 | GEO

Potent and selective PTDSS1 inhibitor targeting collateral lethality against cancer with PTDSS2 deletion [cell_RNA-seq]

Project description:To decipher the underlying mechanism governing selective growth arrest in PTDSS1-inhibited PTDSS2-depleted cancer cells, we analyzed the transcriptomic changes brought about by comparing DMSO treated and DS07551382 treated wild type or PTDSS2-depleted cells.

2022-08-31 | GSE206516 | GEO

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