{"owner": "ArrayExpress Uploader", "ownerprofile_id": "arrayexpress_sid", "id": 7525, "factors": [{"GSM1290674": {"TRANSDUCTION": "shRNA targeting Lacz", "SAMPLE NAME": "1-sp1", "ORGANISM PART": "spleen"}}, {"GSM1290675": {"TRANSDUCTION": "shRNA targeting Lacz", "SAMPLE NAME": "1-sp2", "ORGANISM PART": "spleen"}}, {"GSM1290676": {"TRANSDUCTION": "shRNA targeting Lacz", "SAMPLE NAME": "1-sp3", "ORGANISM PART": "spleen"}}, {"GSM1290677": {"TRANSDUCTION": "shRNA targeting Ppp2r2d", "SAMPLE NAME": "2-sp1", "ORGANISM PART": "spleen"}}, {"GSM1290678": {"TRANSDUCTION": "shRNA targeting Ppp2r2d", "SAMPLE NAME": "2-sp2", "ORGANISM PART": "spleen"}}, {"GSM1290679": {"TRANSDUCTION": "shRNA targeting Ppp2r2d", "SAMPLE NAME": "2-sp3", "ORGANISM PART": "spleen"}}, {"GSM1290680": {"TRANSDUCTION": "shRNA targeting Egr2", "SAMPLE NAME": "3-sp1", "ORGANISM PART": "spleen"}}, {"GSM129068": {"TRANSDUCTION": "shRNA targeting Egr2", "SAMPLE NAME": "3-sp2", "ORGANISM PART": "spleen"}}, {"GSM1290682": {"TRANSDUCTION": "shRNA targeting Egr2", "SAMPLE NAME": "3-sp3", "ORGANISM PART": "spleen"}}, {"GSM1290683": {"TRANSDUCTION": "shRNA targeting Ptpn2", "SAMPLE NAME": "4-sp1", "ORGANISM PART": "spleen"}}, {"GSM1290684": {"TRANSDUCTION": "shRNA targeting Ptpn2", "SAMPLE NAME": "4-sp2", "ORGANISM PART": "spleen"}}, {"GSM1290685": {"TRANSDUCTION": "shRNA targeting Ptpn2", "SAMPLE NAME": "4-sp3", "ORGANISM PART": "spleen"}}, {"GSM1290686": {"TRANSDUCTION": "shRNA targeting Arhgap5", "SAMPLE NAME": "5-sp1", "ORGANISM PART": "spleen"}}, {"GSM1290687": {"TRANSDUCTION": "shRNA targeting Arhgap5", "SAMPLE NAME": "5-sp2", "ORGANISM PART": "spleen"}}, {"GSM1290688": {"TRANSDUCTION": "shRNA targeting Arhgap5", "SAMPLE NAME": "5-sp3", "ORGANISM PART": "spleen"}}, {"GSM1290689": {"TRANSDUCTION": "shRNA targeting Alk", "SAMPLE NAME": "6-sp1", "ORGANISM PART": "spleen"}}, {"GSM1290690": {"TRANSDUCTION": "shRNA targeting Alk", "SAMPLE NAME": "6-sp2", "ORGANISM PART": "spleen"}}, {"GSM129069": {"TRANSDUCTION": "shRNA targeting Alk", "SAMPLE NAME": "6-sp3", "ORGANISM PART": "spleen"}}, {"GSM1290692": {"TRANSDUCTION": "shRNA targeting Lacz", "SAMPLE NAME": "1-tu1", "ORGANISM PART": "Tumor"}}, {"GSM1290693": {"TRANSDUCTION": "shRNA targeting Lacz", "SAMPLE NAME": "1-tu2", "ORGANISM PART": "Tumor"}}, {"GSM1290694": {"TRANSDUCTION": "shRNA targeting Lacz", "SAMPLE NAME": "1-tu3", "ORGANISM PART": "Tumor"}}, {"GSM1290695": {"TRANSDUCTION": "shRNA targeting Ppp2r2d", "SAMPLE NAME": "2-tu1", "ORGANISM PART": "Tumor"}}, {"GSM1290696": {"TRANSDUCTION": "shRNA targeting Ppp2r2d", "SAMPLE NAME": "2-tu2", "ORGANISM PART": "Tumor"}}, {"GSM1290697": {"TRANSDUCTION": "shRNA targeting Ppp2r2d", "SAMPLE NAME": "2-tu3", "ORGANISM PART": "Tumor"}}, {"GSM1290698": {"TRANSDUCTION": "shRNA targeting Egr2", "SAMPLE NAME": "3-tu1", "ORGANISM PART": "Tumor"}}, {"GSM1290699": {"TRANSDUCTION": "shRNA targeting Egr2", "SAMPLE NAME": "3-tu2", "ORGANISM PART": "Tumor"}}, {"GSM1290700": {"TRANSDUCTION": "shRNA targeting Egr2", "SAMPLE NAME": "3-tu3", "ORGANISM PART": "Tumor"}}, {"GSM129070": {"TRANSDUCTION": "shRNA targeting Ptpn2", "SAMPLE NAME": "4-tu1", "ORGANISM PART": "Tumor"}}, {"GSM1290702": {"TRANSDUCTION": "shRNA targeting Ptpn2", "SAMPLE NAME": "4-tu2", "ORGANISM PART": "Tumor"}}, {"GSM1290703": {"TRANSDUCTION": "shRNA targeting Ptpn2", "SAMPLE NAME": "4-tu3", "ORGANISM PART": "Tumor"}}, {"GSM1290704": {"TRANSDUCTION": "shRNA targeting Arhgap5", "SAMPLE NAME": "5-tu1", "ORGANISM PART": "Tumor"}}, {"GSM1290705": {"TRANSDUCTION": "shRNA targeting Arhgap5", "SAMPLE NAME": "5-tu2", "ORGANISM PART": "Tumor"}}, {"GSM1290706": {"TRANSDUCTION": "shRNA targeting Arhgap5", "SAMPLE NAME": "5-tu3", "ORGANISM PART": "Tumor"}}, {"GSM1290707": {"TRANSDUCTION": "shRNA targeting Alk", "SAMPLE NAME": "6-tu1", "ORGANISM PART": "Tumor"}}, {"GSM1290708": {"TRANSDUCTION": "shRNA targeting Alk", "SAMPLE NAME": "6-tu2", "ORGANISM PART": "Tumor"}}, {"GSM1290709": {"TRANSDUCTION": "shRNA targeting Alk", "SAMPLE NAME": "6-tu3", "ORGANISM PART": "Tumor"}}], "pop_total": 0, "platform": 6, "summary_wrapped": "Recent work has shown that cytotoxic T cells play a central role in immune-mediated control of cancers1-3, and monoclonal antibodies that...", "pubmed_id": 24476824, "geo_gse_id": "E-GEOD-53388", "owner_profile": "/profile/8773/arrayexpressuploader", "factor_count": 3, "sample_count": 36, "tags": ["cell", "central", "deep", "melanoma", "spleen"], "lastmodified": "Dec.12, 2014", "is_default": false, "geo_id_plat": "E-GEOD-53388_A-AFFY-45", "slug": "immunotherapy-targets-in-tumors", "geo_gds_id": "", "name": "Immunotherapy Targets in Tumors", "created": "Nov.12, 2014", "summary": "Recent work has shown that cytotoxic T cells play a central role in immune-mediated control of cancers1-3, and monoclonal antibodies that target inhibitory receptors on T cells can induce significant clinical benefit in patients despite advanced disease4-6. However, many of the regulatory pathways that result in loss of T cell function within immunosuppressive tumors remain unknown. Here we show that such regulatory mechanisms can be systematically discovered in vivo in the tumor microenvironment. We devised a pool shRNA screening approach aimed at identifying genes that block the function of tumor-infiltrating CD8 T cells. We postulated that shRNAs targeting key inhibitors would enable robust T cell infiltration and proliferation in tumors, despite multiple inhibitory signals. Candidate shRNAs were discovered by transfer of shRNA-transduced T cells into tumor-bearing mice, followed by deep sequencing to quantify the representation of all hairpins in tumors and lymphoid organs. A subset of shRNAs induced T cell accumulation in tumors but not the spleen, demonstrating feasibility of discovering shRNAs with differential action across tissues. One of the targets was Ppp2r2d, a regulatory subunit of the family of PP2A phosphatases7. Control shRNA-transduced T cells underwent apoptosis upon recognition of melanoma cells, while Ppp2r2d shRNA-transduced T cells accumulated in tumors due to enhanced proliferation and reduced apoptosis. Ppp2r2d shRNAexpressing T cells also significantly delayed tumor growth. This in vivo approach has wide applications to dissect complex immune functions in relevant tissue microenvironments. OT-I derived T cells were transduced with shRNA's and adoptively transferred to B16 tumor bearing mice. Following incubation the T cells were purified from either tumors or spleens. The shRNA's targeted either a control gene (LacZ) or one of 5 selected genes found to regulate the presence of T cells in tumors vs in spleen", "source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-53388", "species": "mouse", "sample_source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-53388/samples/"}