ENAapplication/xmlftp://primary200OKGenomicsDeanG, Department of Drug Discovery Medicine, Kyoto Universityhttps://www.ebi.ac.uk/ena/browser/view/PRJNA717664Mus musculusThe discovery of immune checkpoint inhibitor (ICI) has highlighted the clinical importance of immune evasion in cancer. However, only a fraction of cancer patients show response to ICI, raising a question on immune suppression mechanisms other than immune checkpoint. In this study, we examined the role of the lipid inflammatory mediator PGE2 in immune evasion of the ICI-insensitive Lewis Lung Carcinoma line 1 (LLC1) mouse model. Inhibition of PGE receptors, EP2 and EP4, significantly suppressed tumor growth through the modulation of host immune cells. Single cell RNA-sequencing analysis revealed that EP2/4 inhibition elicited anti-tumor immunity through the reprogramming of inflammatory myeloid cells by downregulating expression of genes in NFB signaling and actions and suppression of the mregDC-regulatory T cell axis by downregulating genes associated with regulatory T cell recruitment and activation. Taken together, our work suggests that PGE2-EP2/EP4 signaling induces proinflammatory myeloid and tolerogenic lymphoid environments in ICI-insensitive tumors, which is amenable to EP2 and EP4 inhibitors.. Overall design: Using 10x genomics to measure single-cell RNA sequence (scRNA-seq) to comprehensively characterize the tumor immune microenvironment in mouse LLC1 tumor syngeneic transplantation model from EP2 and EP4 antagonists treatment and Treg depletion.xref:PubMed:35675777ENA11alpha, second cervical vertebra, Myeloid, Neoplasms, Ptgerep2, Benign Neoplasm, Prostin E2, (Z)-7-((1R, stalk, 13E)-(15S)-11alpha, E2alpha, Tumor, Malignant, EP2C, (E, EP2D, Prostenone, 11, EDDM2B, Minprostin E2, Gel, 15-Dihydroxy-9-oxoprosta-5, HE2C, Alleviating interaction, 13-dien-1-oic acid, Prostaglandin E2alpha, Cervidil, dinoprostonum, Spag11, Dinoproston, 15-Dihydroxy-9-oxoprost-13-enoate, Minprositin E2, Z)-(1R, Immune Processes, Immune Responses, Prostaglandin E2, E)-3-hydroxyoct-1-enyl)-5-oxocyclopentyl)hept-5-enoic acid, Malignancy, alpha-beta regulatory T-cell, CD4-positive, sperm antigen E2, 15S)-11, Cerviprime, regulatory T-cell, suppressive genetic interaction (sensu inequality), suppressor T cell, culm, Ep2e, 2R, Neoplasias, 13E, Immune Response, Immune, suppressor T-lymphocyte, Prepidil Gel, epididymis-specific protein 2, 3R)-7-(3-Hydroxy-2-((3S)-(3-hydroxy-1-octenyl))-5-oxocyclopentyl)-5-heptenoic acid, e2, Malignancies, (15S)-prostaglandin E2, Enzaprost E, U 12062, Immune Process, Myeloid Cell, single organism signaling, Cancer, Tumors, Prosta-5, regulatory T lymphocyte, Malignant Neoplasm, Process, SPAG11, axis, E2, 13-dienoate, C2 vertebra, Cell, Prostin, alpha-beta regulatory T-lymphocyte, Prostaglandin, human epididymis-specific protein 2, Benign, 15-dihydroxy-9-oxo-, Bin1b, regulatory T-lymphocyte, Neoplasm, dinoprostona, dinoprostone, U-12062, CD25-positive, PGE2 alpha, Prostenon, U-12, Prostarmon E, 15-dihydroxy-9-oxoprosta-5, E2 alpha, suppressor T lymphocyte, Prostaglandin E2 alpha, Prepidil, HE2, Benign Neoplasms, alpha, Cancers, 15S)-, Glandin-E2, PGE2alpha, Malignant Neoplasms, PGE2, Cerviprost, suppressor T-cell, 3R)-3-hydroxy-2-((S, EP2, Treg, cervical vertebra 2., signalling process, Propess, 062, (5Z, Cells, Response, alpha-beta regulatory T lymphocyte, other neoplasm, Neoplasia11alpha, second cervical vertebra, Myeloid, Neoplasms, Ptgerep2, Benign Neoplasm, Prostin E2, (Z)-7-((1R, stalk, 13E)-(15S)-11alpha, E2alpha, Tumor, Malignant, EP2C, (E, EP2D, Prostenone, 11, EDDM2B, Minprostin E2, Gel, 15-Dihydroxy-9-oxoprosta-5, HE2C, Alleviating interaction, 13-dien-1-oic acid, Prostaglandin E2alpha, Cervidil, dinoprostonum, Spag11, Dinoproston, 15-Dihydroxy-9-oxoprost-13-enoate, Minprositin E2, Z)-(1R, Immune Processes, Immune Responses, Prostaglandin E2, E)-3-hydroxyoct-1-enyl)-5-oxocyclopentyl)hept-5-enoic acid, Malignancy, alpha-beta regulatory T-cell, CD4-positive, sperm antigen E2, 15S)-11, Cerviprime, regulatory T-cell, suppressive genetic interaction (sensu inequality), suppressor T cell, culm, Ep2e, 2R, Neoplasias, 13E, Immune Response, Immune, suppressor T-lymphocyte, Prepidil Gel, epididymis-specific protein 2, 3R)-7-(3-Hydroxy-2-((3S)-(3-hydroxy-1-octenyl))-5-oxocyclopentyl)-5-heptenoic acid, e2, Malignancies, (15S)-prostaglandin E2, Enzaprost E, U 12062, Immune Process, Myeloid Cell, single organism signaling, Cancer, Tumors, Prosta-5, regulatory T lymphocyte, Malignant Neoplasm, Process, SPAG11, axis, E2, 13-dienoate, C2 vertebra, Cell, Prostin, alpha-beta regulatory T-lymphocyte, Prostaglandin, human epididymis-specific protein 2, Benign, 15-dihydroxy-9-oxo-, Bin1b, regulatory T-lymphocyte, Neoplasm, dinoprostona, dinoprostone, U-12062, CD25-positive, PGE2 alpha, Prostenon, U-12, Prostarmon E, 15-dihydroxy-9-oxoprosta-5, E2 alpha, suppressor T lymphocyte, Prostaglandin E2 alpha, Prepidil, HE2, Benign Neoplasms, alpha, Cancers, 15S)-, Glandin-E2, PGE2alpha, Malignant Neoplasms, PGE2, Cerviprost, suppressor T-cell, 3R)-3-hydroxy-2-((S, EP2, Treg, cervical vertebra 2., signalling process, Propess, 062, (5Z, Cells, Response, alpha-beta regulatory T lymphocyte, other neoplasm, NeoplasiafalseInhibition of PGE2-EP2/EP4 signaling elicits anti-tumor immunity through reprograming of inflammatory myeloid cells and suppression of mRegDC-Treg axisInhibition of PGE2-EP2/EP4 signaling elicits anti-tumor immunity through reprograming of inflammatory myeloid cells and suppression of mRegDC-Treg axis2025-09-242022-06-16PRJNA717664GSE1696881009035675777