The activation of TLR-MyD88 (Toll like receptor- Myeloid differentiation factor 88) signaling within T cells functions as a potent costimulatory signal that boosts antitumor and antiviral responses. However, the molecular mechanisms underlying the costimulatory processes are poorly understood. We compared microarray gene analysis data between TLR1-TLR2 stimulated and unstimulated T cell receptor transgenic pmel and MyD88-/-pmel CD8+ T cells and identified changes in the expression levels of several TNF family members. In particular, TLR-stimulation increased 4-1BB levels in pmel but not in MyD88-/-pmel T cells. A link between 4-1BB and TLR1-TLR2 signaling in CD8+ T cells was highlighted by in fact that 4-1BB-/- T cells exhibited suboptimal responses to TLR1-TLR2 agonist, but responded normally to CD28 or OX40 costimulation. Moreover, blocking 4-1BB signaling with antibodies also hindered the costimulatory effects of the TLR1-TLR2 agonist. The elevated levels of 4-1BB transcripts in TLR1-TLR2stimulated cells were not due to increased mRNA stability nor increased histone activation but instead were associated with increased binding of p65 and c-Jun to two distinct 4-1BB promoter sites. Combining TLR1-TLR2 ligand with an agonistic anti-4-1BB antibody enhanced the antitumor activity in mice with established melanoma tumors. These studies reveal that the costimulatory effects of TLR1-TLR2 signaling in CD8+ T cells are in part mediated by 4-1BB and are important for mounting an effective antitumor immune response.
Cross-talk between 4-1BB and TLR1-TLR2 Signaling in CD8+ T Cells Regulates TLR2's Costimulatory Effects.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Regulation of Virus-Associated Lymphoma Growth and Gene Expression by Bacterial Quorum-Sensing Molecules.
Cell line, Treatment
View SamplesKSHV-related primary effusion lymphoma is mostly seen in immunocompromised individuals such as HIV+ patients, who frequently suffering polymicrobial infections including different opportunistic pathogens. It is interesting to explore the host gene profile in PEL altered by bacterial quorum sensing molecules, the key systems regulating virulence factors in many bacteria.
Regulation of Virus-Associated Lymphoma Growth and Gene Expression by Bacterial Quorum-Sensing Molecules.
Cell line, Treatment
View SamplesKSHV-related primary effusion lymphoma is mostly seen in immunocompromised individuals such as HIV+ patients, who frequently suffering polymicrobial infections including different opportunistic pathogens. It is interesting to explore the host gene profile in PEL altered by bacterial quorum sensing molecules, the key systems regulating virulence factors in many bacteria.
Regulation of Virus-Associated Lymphoma Growth and Gene Expression by Bacterial Quorum-Sensing Molecules.
Cell line, Treatment
View SamplesKSHV-related primary effusion lymphoma is mostly seen in immunocompromised individuals such as HIV+ patients, who frequently suffering polymicrobial infections including different opportunistic pathogens. It is interesting to explore the host gene profile in PEL altered by bacterial quorum sensing molecules, the key systems regulating virulence factors in many bacteria.
Regulation of Virus-Associated Lymphoma Growth and Gene Expression by Bacterial Quorum-Sensing Molecules.
Cell line, Treatment
View SamplesKSHV-related primary effusion lymphoma is mostly seen in immunocompromised individuals such as HIV+ patients, who frequently suffering polymicrobial infections including different opportunistic pathogens. It is interesting to explore the host gene profile in PEL altered by bacterial quorum sensing molecules, the key systems regulating virulence factors in many bacteria.
Regulation of Virus-Associated Lymphoma Growth and Gene Expression by Bacterial Quorum-Sensing Molecules.
Cell line, Treatment
View SamplesPrimary effusion lymphoma (PEL) is a rare B-cell malignancy that originates from B cells latently infected with Kaposis sarcoma-associated herpesvirus (KSHV, also known as human herpesvirus-8, HHV8). Our previous data indicated that several exogenous ceramide and dh-ceramide species, such as C18-Cer and dhC16-Cer, also displayed effective anti-cancer activities for KSHV+ PEL in vitro and in vivo. However, the underlying mechanisms for exogenous ceramide killing PEL cells still require further investigation, which will be helpful to better understand PEL pathogenesis and identify more potential therapeutic targets. In the current study, we used Illumina microarray to determine the altered gene profile in KSHV+ PEL cell-line, BCBL-1 exposure to dhC16-Cer.
Up-regulation of tumor suppressor genes by exogenous dhC16-Cer contributes to its anti-cancer activity in primary effusion lymphoma.
Cell line, Treatment
View SamplesThe Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi sarcoma (KS), the most common HIV/AIDS-associated tumor worldwide. Transmission routes of KSHV in the general population are poorly understood. Whereas sexual transmission appears to be common in homosexual men, the evidence for heterosexual transmission is less convincing. In fact, KSHVDNA sequences have been detected in the prostate, semen, and in the female genital tract. Persistent infection with high-risk human papillomavirus (HPV) is the major risk factor and is a requirement for the development of cervical cancer. However, it remains unknown the interaction between KSHV and HPV, and the contribution of KSHV to cervical cancer development and pathogenesis. In the present study, we used Illumina microarray to detect the global gene profile altered in KSHV-infected siHa cervical cancer cell-line containing integrated HPV16 genome.
KSHV co-infection down-regulates HPV16 E6 and E7 from cervical cancer cells.
Cell line
View SamplesThe Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi sarcoma (KS), the most common HIV/AIDS-associated tumor worldwide. Involvement of the oral cavity portends a poor prognosis for patients with KS, but mechanisms for KSHV regulation of the oral tumor microenvironment are largely unknown. Infiltrating fibroblasts are found with KS lesions, and KSHV establishes latent infection within human primary fibroblasts in vitro, but contributions for KSHV-infected fibroblasts to the KS microenvironment have not been previously characterized. In the present study, we used Illumina microarray to detect the global gene profile altered in KSHV-infected primary human fibroblasts (PDLF and HGF) isolated from the oral cavity.
Transcriptomic analysis of KSHV-infected primary oral fibroblasts: The role of interferon-induced genes in the latency of oncogenic virus.
Specimen part
View SamplesTo identify potential biological targets of the TGFß pathway involved in AVM formation, we performed RNA-seq on endothelial cells (ECs) isolated from a Smad4 inducible, EC specific knockout (Smad4-iECKO; Smad4f/f;Cdh5-CreERT2) mouse model that develops retinal AVMs. Overall design: We sequenced a total of 6 samples. We used three wild type samples (Smad4f/f- samples names: Lit38s45, Lit38s6, Lit40s56) and three mutant samples (Smad4f/f;Cdh5-CreERT2- sample names: Lit38s12, Lit38s37, Lit40s12). For more detailed information please see supplemental document: GSE116230_Smad4ff_vs_Smad4iECKO.report.pdf
Angiopoietin-2 Inhibition Rescues Arteriovenous Malformation in a Smad4 Hereditary Hemorrhagic Telangiectasia Mouse Model.
Specimen part, Cell line, Subject
View Samples