STANDARD_NAME GSE29164_UNTREATED_VS_CD8_TCELL_AND_IL12_TREATED_MELANOMA_DAY7_DN SYSTEMATIC_NAME M8498 COLLECTION C7:IMMUNESIGDB MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/GSE29164_UNTREATED_VS_CD8_TCELL_AND_IL12_TREATED_MELANOMA_DAY7_DN NAMESPACE HUMAN_GENE_SYMBOL DESCRIPTION_BRIEF Genes down-regulated in B16 melanoma (day 7): untreated versus mock treatment during adoptive transfer therapy. DESCRIPTION_FULL Myeloid-derived cells comprising the tumor stroma represent a heterogeneous population of cells critical to the structure, function and growth of established cancers. We have recently found that engineering tumor-specific CD8+ T cells to secrete IL-12 (IL-12TD) can lead to striking improvements in T-cell activity against established melanomas in murine models. Surprisingly, IL-12-dependent enhancement of CD8+ T-cell anti-tumor function did not occur through direct ligation of receptors on lymphocytes or NK cells. Instead, IL-12 sensitized host bone marrow-derived tumor-stromal cells, partly through interferon-gamma, to indirectly enhance the effects of adoptively-transferred T cells. Direct presentation of antigen by tumor was not necessary, but MHC class I expression on endogenous cells was essential for IL-12 mediated anti-tumor enhancements. Upon successful treatment with IL-12TD cells, we observed the selective elimination of tumor-infiltrating CD11b+ F4/80+ macrophages, CD11b+/ClassII+/CD11c+ dendritic cells and CD11b+/Ly6C+/Ly6G- but not CD11b+/Ly6C+/Ly6G+ myeloid-derived suppressor cells within regressing lesions. These results are consistent with a model whereby IL-12 triggers the maturation of myeloid-derived cells into competent antigen cross-presenting cells. Licensed recognition of these antigens by effector T cells may in turn trigger the collapse of the tumor stroma and aid in the regression of large vascularized lesions. PMID 22056381 GEOID GSE29164 AUTHORS Kerkar SP,Goldszmid RS,Muranski P,Chinnasamy D,Yu Z,Reger RN,Leonardi AJ,Morgan RA,Wang E,Marincola FM,Trinchieri G,Rosenberg SA,Restifo NP CONTRIBUTOR Jernej Godec CONTRIBUTOR_ORG Dana-Farber Cancer Institute EXACT_SOURCE GSE29164_2440_200_DN FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS AANAT,ABCB1,ABCC9,ABCE1,ACOT13,ADAMTS1,AKT1,AP1B1,APOL2,ARMCX2,ASB12,ASB2,ATPIF1,BAG1,C14orf180,C17orf81,C1orf187,C1orf53,C1orf54,C20orf54,C20orf7,C22orf28,CAPSL,CARD10,CAV1,CCDC102A,CCDC56,CCR9,CD244,CD274,CD7,CDKN1A,CHST15,CHURC1,CLDN5,CLEC10A,CLU,CMTM8,COMMD3,COX6C,COX8A,CTLA4,CX3CL1,CXCL2,CXCR3,DARC,DLL4,DNAJB13,DNAJB2,DPYSL5,EAPP,EBNA1BP2,ECE1,ECE2,ELAC2,ETV5,FABP1,FAM158A,FAM162A,FAM195B,FAM71B,FAM98C,FCRL1,FGD6,FGFR4,FLRT3,FYN,GAA,GDF9,GP9,GPANK1,GPCPD1,GPD2,GPR132,GRAP,GRM1,GSX1,GTF2F2,HIBADH,HM13,HOMER2,HOXD12,HRASLS5,HSPB1,HSPBP1,ICAM1,IFT43,IL12B,IL21R,IL7R,IMMP2L,IPCEF1,ITPK1,JUNB,KBTBD13,KITLG,MARCKSL1,MARCO,MARVELD2,MGAT3,MMP9,MPP2,MPST,MREG,MRPL48,MRVI1,MTMR10,MYC,NAAA,NAGA,NANOS1,NCOA7,NCRNA00116,NDUFA2,NDUFA6,NDUFS6,NPM1,NPR3,NUCB2,NXT1,PAK1,PALLD,PAQR4,PARD6A,PCBD2,PCP4,PDCD4,PDLIM2,PFDN5,PFN1,PGLYRP1,PHLDA1,PIGP,PIGU,PIK3IP1,PIN4,PKIB,PLEKHG6,PMVK,PPP3CC,PPT1,PRAF2,PSTPIP1,PTOV1,PTRH2,PVT1,RAB11FIP4,RAB8A,RABAC1,RABL5,RBPMS2,RHOC,RNF165,RPL22L1,RTCD1,RWDD1,SALL3,SCGN,SEC61G,SERINC4,SERPINB9,SFTPD,SGCE,SGSM3,SIGIRR,SLC25A25,SLC25A33,SLC41A1,SNN,SNRPF,SPAG9,SPIB,SPP1,SQSTM1,SSSCA1,ST8SIA6,STAP2,TAF4B,TAP2,TES,THYN1,TIMP3,TM2D1,TMEM123,TNFRSF8,TRIB1,TRIM7,TRIT1,TSPAN9,UNC119,USE1,UST,VAMP8,VEGFC,VPS37B,WDR34,YIF1B,ZBTB10,ZMAT5,ZNRD1 GENE_SYMBOLS AANAT,ABCB1,ABCC9,ABCE1,ACOT13,ADAMTS1,AKT1,AP1B1,APOL2,ARMCX2,ASB12,ASB2,ATP5IF1,BAG1,C14orf180,ELP5,DRAXIN,C1orf53,C1orf54,SLC52A3,NDUFAF5,RTCB,CAPSL,CARD10,CAV1,CCDC102A,COA3,CCR9,CD244,CD274,CD7,CDKN1A,CHST15,CHURC1,CLDN5,CLEC10A,CLU,CMTM8,COMMD3,COX6C,COX8A,CTLA4,CX3CL1,CXCL2,CXCR3,ACKR1,DLL4,DNAJB13,DNAJB2,DPYSL5,EAPP,EBNA1BP2,ECE1,ECE2,ELAC2,ETV5,FABP1,EMC9,FAM162A,MCRIP1,GARIN3,FAM98C,FCRL1,FGD6,FGFR4,FLRT3,FYN,GAA,GDF9,GP9,GPANK1,GPCPD1,GPD2,GPR132,GRAP,GRM1,GSX1,GTF2F2,HIBADH,HM13,HOMER2,HOXD12,PLAAT5,HSPB1,HSPBP1,ICAM1,IFT43,IL12B,IL21R,IL7R,IMMP2L,IPCEF1,ITPK1,JUNB,KBTBD13,KITLG,MARCKSL1,MARCO,MARVELD2,MGAT3,MMP9,MPP2,MPST,MREG,MRPL48,IRAG1,MTMR10,MYC,NAAA,NAGA,NANOS1,NCOA7,MTLN,NDUFA2,NDUFA6,NDUFS6,NPM1,NPR3,NUCB2,NXT1,PAK1,PALLD,PAQR4,PARD6A,PCBD2,PCP4,PDCD4,PDLIM2,PFDN5,PFN1,PGLYRP1,PHLDA1,PIGP,PIGU,PIK3IP1,PIN4,PKIB,PLEKHG6,PMVK,PPP3CC,PPT1,PRAF2,PSTPIP1,PTOV1,PTRH2,PVT1,RAB11FIP4,RAB8A,RABAC1,IFT22,RBPMS2,RHOC,RNF165,RPL22L1,RTCA,RWDD1,SALL3,SCGN,SEC61G,SERINC4,SERPINB9,SFTPD,SGCE,SGSM3,SIGIRR,SLC25A25,SLC25A33,SLC41A1,SNN,SNRPF,SPAG9,SPIB,SPP1,SQSTM1,ZNRD2,ST8SIA6,STAP2,TAF4B,TAP2,TES,THYN1,TIMP3,TM2D1,TMEM123,TNFRSF8,TRIB1,TRIM7,TRIT1,TSPAN9,UNC119,USE1,UST,VAMP8,VEGFC,VPS37B,DYNC2I2,YIF1B,ZBTB10,ZMAT5,POLR1H FOUNDER_NAMES