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Series GSE29164 Query DataSets for GSE29164
Status Public on Apr 23, 2012
Title IL-12 induces myeloid cells in situ to cross-present antigen
Organism Mus musculus
Experiment type Expression profiling by array
Summary 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.
 
Overall design Samples were collected at 3 days and 7 days from tumors treated in-vivo with no treatment, Mock pmel-1 CD8+ cell treatment, or IL-12 pmel-1 CD8+ cell treatment. There were 4 biological replicates of each sample type. There were a total of 24 samples.
 
Citation(s) 22056381
Submission date May 09, 2011
Last update date Mar 04, 2019
Contact name Francesco Maria Marincola
E-mail(s) [email protected]
Phone 301-793-8210
Organization name Sidra Medical and Research Center
Street address Al Nasr Tower, AL Corniche Street, PO Box 26999
City Doha
ZIP/Postal code PO Box 26999
Country Qatar
 
Platforms (1)
GPL6246 [MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version]
Samples (24)
GSM721735 No Treatment - 3 days - repeat 1 - mAdbID:115862
GSM721736 No Treatment - 3 days - repeat 2 - mAdbID:115863
GSM721737 No Treatment - 3 days - repeat 3 - mAdbID:115864
Relations
BioProject PRJNA140083

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Supplementary file Size Download File type/resource
GSE29164_RAW.tar 89.4 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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