Standard name |
WORSCHECH_TUMOR_EVASION_AND_TOLEROGENICITY_UP |
Systematic name |
M1989 |
Brief description |
Selected genes with immunologic function which were reciprocally changed in evasion and tolerogenic tumor models. |
Full description or abstract |
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. |
Collection |
C2: Curated CGP: Chemical and Genetic Perturbations |
Source publication |
Pubmed 18381452 Authors: Worschech A,Kmieciak M,Knutson KL,Bear HD,Szalay AA,Wang E,Marincola FM,Manjili MH |
Exact source |
Evasion > 1 & Tolerogenic < 1 |
Related gene sets |
(show 3 additional gene sets from the source publication)
(show 41 gene sets from the same authors)
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External links |
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Filtered by similarity ?
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Source species |
Mus musculus |
Contributed by |
Arthur Liberzon (MSigDB Team) |
Source platform or identifier namespace |
MOUSE_GENE_SYMBOL |
Dataset references |
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format: grp | gmt | xml | json | TSV metadata |
Compute overlaps ? |
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Compendia expression profiles ? |
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
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Advanced query |
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these 31 genes
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Gene families ? |
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31 genes by gene family
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Show members |
(show 33 source identifiers mapped to 31 genes)
Source Id |
NCBI (Entrez) Gene Id |
Gene Symbol |
Gene Description |
Blnk |
29760 |
BLNK |
B cell linker [Source:HGNC Symbol;Acc:HGNC:1... |
Bok |
666 |
BOK |
BCL2 family apoptosis regulator BOK [Source:... |
Ccl2 |
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Ccl4 |
6351 |
CCL4 |
C-C motif chemokine ligand 4 [Source:HGNC Sy... |
Ccl6 |
6368 |
CCL23 |
C-C motif chemokine ligand 23 [Source:HGNC S... |
Ccr7 |
1236 |
CCR7 |
C-C motif chemokine receptor 7 [Source:HGNC ... |
Cx3cl1 |
6376 |
CX3CL1 |
C-X3-C motif chemokine ligand 1 [Source:HGNC... |
Cxcl10 |
3627 |
CXCL10 |
C-X-C motif chemokine ligand 10 [Source:HGNC... |
Cxcl9 |
4283 |
CXCL9 |
C-X-C motif chemokine ligand 9 [Source:HGNC ... |
Ifnar1 |
3454 |
IFNAR1 |
interferon alpha and beta receptor subunit 1... |
Ifnb1 |
3456 |
IFNB1 |
interferon beta 1 [Source:HGNC Symbol;Acc:HG... |
Ifrd1 |
3475 |
IFRD1 |
interferon related developmental regulator 1... |
Igtp |
345611 |
IRGM |
immunity related GTPase M [Source:HGNC Symbo... |
Il12b |
3593 |
IL12B |
interleukin 12B [Source:HGNC Symbol;Acc:HGNC... |
Il13 |
3596 |
IL13 |
interleukin 13 [Source:HGNC Symbol;Acc:HGNC:... |
Il17d |
53342 |
IL17D |
interleukin 17D [Source:HGNC Symbol;Acc:HGNC... |
Il23r |
149233 |
IL23R |
interleukin 23 receptor [Source:HGNC Symbol;... |
Il2rg |
3561 |
IL2RG |
interleukin 2 receptor subunit gamma [Source... |
Il4 |
3565 |
IL4 |
interleukin 4 [Source:HGNC Symbol;Acc:HGNC:6... |
Il4i1 |
259307 |
IL4I1 |
interleukin 4 induced 1 [Source:HGNC Symbol;... |
Il6 |
3569 |
IL6 |
interleukin 6 [Source:HGNC Symbol;Acc:HGNC:6... |
Il7r |
3575 |
IL7R |
interleukin 7 receptor [Source:HGNC Symbol;A... |
Il9 |
3578 |
IL9 |
interleukin 9 [Source:HGNC Symbol;Acc:HGNC:6... |
Irf7 |
3665 |
IRF7 |
interferon regulatory factor 7 [Source:HGNC ... |
Lcp2 |
3937 |
LCP2 |
lymphocyte cytosolic protein 2 [Source:HGNC ... |
Ly6d |
8581 |
LY6D |
lymphocyte antigen 6 family member D [Source... |
Nfkb1 |
4790 |
NFKB1 |
nuclear factor kappa B subunit 1 [Source:HGN... |
Pias2 |
9063 |
PIAS2 |
protein inhibitor of activated STAT 2 [Sourc... |
Pias3 |
10401 |
PIAS3 |
protein inhibitor of activated STAT 3 [Sourc... |
Stat4 |
6775 |
STAT4 |
signal transducer and activator of transcrip... |
Tlr11 |
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Vpreb3 |
29802 |
VPREB3 |
V-set pre-B cell surrogate light chain 3 [So... |
Xcl1 |
6375 |
XCL1 |
X-C motif chemokine ligand 1 [Source:HGNC Sy... |
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Version history |
3.1: First introduced
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