STANDARD_NAME WORSCHECH_TUMOR_EVASION_AND_TOLEROGENICITY_DN SYSTEMATIC_NAME M1990 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WORSCHECH_TUMOR_EVASION_AND_TOLEROGENICITY_DN NAMESPACE MOUSE_GENE_SYMBOL DESCRIPTION_BRIEF Selected genes with immunologic function which were reciprocally changed in evasion and tolerogenic tumor models. DESCRIPTION_FULL We have previously shown T-cell-mediated rejection of the neu-overexpressing mammary carcinoma cells (MMC) in wild-type FVB mice. However, following rejection of primary tumors, a fraction of animals experienced a recurrence of a neu antigen-negative variant (ANV) of MMC (tumor evasion model) after a long latency period. In the present study, we determined that T cells derived from wild-type FVB mice can specifically recognize MMC by secreting IFN-gamma and can induce apoptosis of MMC in vitro. Neu transgenic (FVBN202) mice develop spontaneous tumors and cannot reject it (tumor tolerance model). To dissect the mechanisms associated with rejection or tolerance of MMC tumors, we compared transcriptional patterns within the tumor microenvironment of MMC undergoing rejection with those that resisted it either because of tumor evasion/antigen loss recurrence (ANV tumors) or because of intrinsic tolerance mechanisms displayed by the transgenic mice. Gene profiling confirmed that immune rejection is primarily mediated through activation of IFN-stimulated genes and T-cell effector mechanisms. The tumor evasion model showed combined activation of Th1 and Th2 with a deviation toward Th2 and humoral immune responses that failed to achieve rejection likely because of lack of target antigen. Interestingly, the tumor tolerance model instead displayed immune suppression pathways through activation of regulatory mechanisms that included in particular the overexpression of interleukin-10 (IL-10), IL-10 receptor, and suppressor of cytokine signaling (SOCS)-1 and SOCS-3. These data provide a road map for the identification of novel biomarkers of immune responsiveness in clinical trials. PMID 18381452 GEOID AUTHORS Worschech A,Kmieciak M,Knutson KL,Bear HD,Szalay AA,Wang E,Marincola FM,Manjili MH CONTRIBUTOR Arthur Liberzon CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Evasion < 1 & Tolerogenic > 1 FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS Bak1,Ifngr1,Ifrg15,Il10,Il10rb,Il1r2,Irf1,Irf3,Irf6,Lsp1,Socs1,Socs3,Tank,Tlr6 GENE_SYMBOLS BAK1,IFNGR1,TOR1AIP2,IL10,IL10RB,IL1R2,IRF1,IRF3,IRF6,LSP1,SOCS1,SOCS3,TANK,TLR6 FOUNDER_NAMES