Similar Datasets
Project description:The goal of this study was to examine differences in gene expression of tumor specific CD8 T cells in an in vivo tumor mouse model after inhibition of galectin-3 protein expression by genetic knockout. Galectin-3 is thought to modulate CD8 T cell response by cross-linking cell surface glycoproteins Galectin-3 is a 31 kD carbohydrate-binding lectin that is over-expressed by many human malignancies. It also modulates T cell responses through a diverse array of mechanisms including induction of apoptosis, TCR cross linking in CD8+ T cells, and T cell receptor (TCR) down regulation in CD4+ T cells. We found that patients responding to a granulocyte-macrophage colony-stimulating factor (GM-CSF) secreting allogeneic pancreatic tumor vaccine developed post immunization antibody responses to galectin-3 on a proteomic screen. We used the HER-2/neu (neu-N) transgenic mouse model to study galectin-3 binding on adoptively transferred high avidity neu-specific CD8+ T cells derived from TCR transgenic mice. Here, we show that galectin-3 binds preferentially to activated antigen-committed CD8+ T cells only in the tumor microenvironment (TME). Galectin-3 deficient mice exhibit improved CD8+ T cell effector function and increased expression of several inflammatory genes when compared with wild type (WT) mice. We also show that galectin-3 binds to LAG-3, and LAG-3 expression is necessary for galectin-3 mediated suppression of CD8+ T cells in vitro. Lastly, galectin-3 deficient mice have significantly elevated levels of circulating plasmacytoid dendritic cells (pDCs), which are superior to conventional dendritic cells (cDCs) in activating CD8+ T cells. Binding of galectin-3 to cell-surface glycoproteins on immune cells suppresses a pro-inflammatory immune response. Thus, inhibiting galectin-3 in conjunction with CD8+ T cell directed immunotherapies should enhance the tumor specific immune response. 3 different experimental groups were studied. Galectin-3 WT CD8 T cells adoptively transferred into Galectin-3 WT mice, galectin-3 WT CD8 T cells transferred into galectin-3 KO mice, and finally galectin-3 KO CD8 T cells transferred into galectin-3 KO mice. Galectin-3 WT CD8 T cells transferred into Galectin-3 WT mice were used as the reference group. Four biological replicates were submitted for each group, and adoptively transfered CD8 T cells were isolated 5 days post-adoptive transfer into tumor-bearing mice treated with a whole cell GM-CSF secreting vaccine. Cells were purified by cell sorting on the Thy1.2 surface marker.
2015-02-19 | E-GEOD-59454 | biostudies-arrayexpress
Project description:T cell metabolic fitness plays a pivotal role in anti-tumor immunity and metabolic deregulation causes T cell dysfunction in cancer. We identify that CD36 limits anti-tumor CD8+ T cell effector functions through lipid peroxidation. In murine tumors, oxidized phospholipids (OxPLs) were highly abundant and CD8+ TILs increased uptake and accumulation of lipids and lipid peroxidation. Functionally ‘exhausted’ CD8+ TILs increased CD36 expression and CD36-deficient CD8+ TILs had more robust anti-tumor activity and cytokine production than wild-type cells. We further show that CD36 promotes uptake of oxidized low-density lipoproteins (OxLDL), induces lipid peroxidation in CD8+ TILs, and enhances p38 kinase phosphorylation. Moreover, we found that OxLDL inhibits CD8+ T cell functions in a CD36/p38-dependent manner. Furthermore, glutathione peroxidase 4 (GPX4) over-expression lowers lipid peroxidation and restores functionalities in CD8+ TILs. These results define a key role for an oxidized lipid-CD36-p38 axis in promoting intratumoral CD8+ T cell dysfunction.
2021-03-31 | GSE171194 | GEO
Project description:To elucidate the effect of menin on the differentiation of CD8 T cell, the gene expression were measured in WT and Menin KO CD8 T cells.
2023-07-12 | GSE215391 | GEO
Project description:This experiment was performed to examine transcriptional differences between WT and Tgfbr2 KO antigen-specific CD8 cells activated in established chronic infection.
2022-08-09 | GSE209577 | GEO
Project description:To more specifically determine whether the TEC program is controlled by Notch, we generated molecular definitions of TECs and MPCs by whole transcriptome sequencing of sorted KLRG1-CD127+ and KLRG1+CD127- H-2 Db-NP specific CD8+ T cell populations from wild-type mice. These definitions were used to analyze data derived from RNAseq of splenic H-2 Db-NP+CD8+ T cells from WT and Notch1-2-KO mice 10 days post-infection with A/HKx31.
2014-10-26 | E-MTAB-2999 | biostudies-arrayexpress
Project description:B7S1 negatively regulates T cells and its expression correlates with poor prognosis of cancer patients. In order to understand how B7S1 signaling contributes to dysfunction of CD8+ T cell in the TME, we conducted transcriptional analysis of OVA-specific CD8+ TILs and different TIL subsets from E.G7-bearing WT and B7S1 KO mice (Day 21).
2018-04-03 | GSE110249 | GEO
Project description:Transcriptional profiling of mouse lung tumors comparing Dnmt3a KO/K-ras G12D mutant with Dnmt3a WT/K-ras G12D mutant. The goal is to search for the difference of mRNA abundance between Dnmt3a KO and WT tumors.
2011-10-26 | GSE32415 | GEO
Project description:CD8+ DCs play key role in CD8+ T cell priming, however, the underlying signaling mechansim is unclear. We used a data-driven network-based systems biology approach and identified Hippo signaling kinases as key selective modualtors in CD8+ DCs. We focused on Mst1/Stk4 to further investigate the novel function of Hippo signaling in CD8+ DCs. All transcriptional profies were evalated by microarray. 1) We used microarrays of total DCs in previous (GSE98481) and current studies to reverse engineer a DC-specific signaling interactome (DCI). 2) We integrated DCI with profiles of sorted CD8+ with CD8- DCs to identify signaling drivers of CD8+ DCs. 3) We profiled and compared Mst1/2-KO with WT cells from total, CD8+ and CD8- DCs to understand the mechanism of Mst1 in CD8+ DCs.
2018-06-08 | GSE100772 | GEO
Project description:Transcriptional profiling of mouse lung tumors comparing Dnmt3a KO/K-ras G12D mutant with Dnmt3a WT/K-ras G12D mutant. The goal is to search for the difference of mRNA abundance between Dnmt3a KO and WT tumors. Two-condition experiment, KO vs. WT tissure. Biological replicates: 12.
2011-10-25 | E-GEOD-32415 | biostudies-arrayexpress