Project description:Active suppression of tumor-specific T lymphocytes can limit the immune-surveillance and immunotherapy efficacy. While tumor-recruited CD11b+ myeloid cells are known mediators of tumor-associated immune dysfunction, the true nature of these suppressive cells and the fine biochemical pathways governing their immunosuppressive activity remain elusive. Here we describe a population of circulating CD11b+/IL-4Rα+, inflammatory-type monocytes that is elicited by growing tumors and activated by IFN-γ released from T lymphocytes. CD11b+/IL-4Rα+ cells produce IL-13 and IFN-γ and integrate the downstream signals of these cytokines to trigger the molecular pathways suppressing antigen-activated CD8+ T lymphocytes. Analogous immunosuppressive circuits are active in CD11b+ cells present within the tumor microenvironment. These suppressor cells challenge the current idea that tumor-conditioned immunosuppressive monocytes/macrophages are alternatively activated. Moreover, our data show how the inflammatory response elicited by tumors has detrimental effects on the adaptive immune system and suggest novel approaches for the treatment of tumorinduced immune dysfunctions. Experiment Overall Design: Labeled cRNA extracted from a a total of 9 samples was hybridized to the Affymetrix GeneChip MG-U74Av2 which contains 12,488 probe sets . The 3 control samples represented 3 replicates of RNA extracted from Cd11b cells purified from the spleen of tumor-free mice. The 6 samples obtained from tumor-bearing mice represented 3 replicates each of RNA extracted from Cd11b cells purified from the spleen of tumor-bearing mice. Three out of six samples were incubated for 24 hours in complete medium.
Project description:Myeloid derived suppressor cells (MDSC) in the tumor microenvironment suppress T-cell mediated immune surveillance that clears tumor cells. As such, MDSC promote tumor growth. There are two subtypes of tumor MDSC, CD11b+Ly6ChiLy6G- monocytic MDSC (M-MDSC) , and CD11b+Ly6ClowLy6Ghigh granulocytic MDSC (G-MDSC). Cells with these markers also exist in the spleen of tumor bearing mice or in the spleen of mice with tissue-specific inflammation. Some have argued that the tumor MDSC is an activated version of the spleen MDSC, implying that they are similar to one another. Here we isolated the MDSC subtypes from the RM-1 tumors and from the spleen of mice with prostatic inflammation (n=4 per subtype per tissue, 16 total samples). We then analyzed RNA from these cells to determine how the transcript profile was altered by tissue location and MDSC subtype. Platform: Affymetrix Mouse Gene 1.0 ST v1 Genechip
Project description:Single-cell transcriptome profiling using a 3' droplet-based platform (Chromium,10x Genomics) of CD11b+ cells isolated from the spleen of control and tumor-bearing mice, treated or not with IFN gene therapy.
Project description:Transcriptional profiling of FACS-sorted and splenic control mouse cells, comparing splenic cells from FVBneuN vs Neu+ expressing FVBneuN mice with Gr1+ CD11b+ sorted tumor-infiltrating mononuclear or splenic myeloid-derived suppressor cells 4 groups or conditions. Biological replicates: 2 or 3 per condition. One replicate array per sample. manuscript: van Deventer, H, J Burgents, QP Wu, R Woodford, WJ Brickey, I Allen, E McElvania-Tekippe, J Serody, and J Ting. (2010) The inflammasome component Nlrp3 impairs antitumor vaccine by enhancing the accumulation of tumor-associated myeloid-derived suppressor cells. Cancer Research. variable: cell type: splenic cells from normal FVB-neuN mice, splenic cells from Neu+ tumor-bearing FVB-neuN mice, Gr1+ CD11b+ sorted cells from tumor, Gr1+ CD11b+ sorted cells from spleen repear: biological replicate: #1, #2, #3
Project description:Purpose: To study the alteration of whole transcriptome of Lewis lung carcinoma (LLC) cells after the decreasing of malignant properties of tumor by treatment of tumor-bearing mice with RNase A. Methods: Whole transcriptome profile of Lewis lung carcinoma before and after RNase A treatment were generated by deep sequencing using SOLiD 5.5. The sequence reads were mapped by Bioscope 1.3 software, differential expression was evaluated by Cufflinks v.2.0.1 package. Results: Difference in expression was found for 966 genes. Conclusions: Our study represents the first detailed analysis of alteration of transcriptome of Lewis lung carcinoma after the decrease of malignant prtoperties of the tumor (proliferation and invasion) by RNase A.