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Target Concepts:
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Query: KEGG:D03301 (
PDL
)
658
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Regulation of T cell function in the steady state is mediated by co-inhibitory receptors or immune checkpoints such as PD-1, CTLA-4, TIM-3 and
LAG-3
. Persistent antigen stimulation, during chronic viral infections and cancer, results in sustained expression of multiple co-inhibitory receptors and subsequently poor effector T cell function. Immune checkpoint blockade using monoclonal antibodies against PD-1,
PDL
-1 and CTLA-4 has been implemented as an immunotherapy strategy- resulting in restoration of T cell function and reduction of viral load or tumour growth. Immunomodulatory roles of commonly used cholesterol-lowering medications, atorvastatin and other statins, are widely documented. We have previously shown that atorvastatin can inhibit HIV-1 infection and replication. Here, for the very first time we discovered that atorvastatin also regulates activated T cell function by mediating downregulation of multiple co-inhibitory receptors, which corresponded with increased IL-2 production by stimulated T cells. In addition, we found that atorvastatin treatment reduces expression of mTOR and downstream T cell effector genes. We demonstrate a novel mechanism showing that atorvastatin inhibition of Ras-activated MAPK and PI3K-Akt pathways, and subsequent mTOR signalling promotes gross downregulation of co-inhibitory receptors. Thus, our results suggest that statins may hold particular promise in reinvigorating T cell function in chronic conditions.
...
PMID:Atorvastatin downregulates co-inhibitory receptor expression by targeting Ras-activated mTOR signalling. 2922 84
T cell infiltration of tumors plays an important role in determining colorectal cancer disease progression and has been incorporated into the Immunoscore prognostic tool. In this study, mass cytometry was used to demonstrate a significant increase in the frequency of both conventional CD25
+
FOXP3
+
CD127
lo
regulatory T cells (Tregs) as well as BLIMP-1
+
Tregs in the tumor compared with nontumor bowel (NTB) of the same patients. Network cluster analyses using SCAFFoLD, VorteX, and CITRUS revealed that an increase in BLIMP-1
+
Tregs was a single distinguishing feature of the tumor tissue compared with NTB. BLIMP-1
+
Tregs represented the most significantly enriched T cell population in the tumor compared with NTB. The enrichment of ICOS, CD45RO, PD-1,
PDL
-1,
LAG-3
, CTLA-4, and TIM-3 on BLIMP-1
+
Tregs suggests that BLIMP-1
+
Tregs have a more activated phenotype than conventional Tregs and may play a role in antitumor immune responses.
...
PMID:High-Dimensional Mass Cytometric Analysis Reveals an Increase in Effector Regulatory T Cells as a Distinguishing Feature of Colorectal Tumors. 3072 10
Cancer is the second cause of mortality in the world after cardiovascular disease. Various studies attribute the emergence of therapeutic resistance in tumors to the presence of cancer stem cells or cancer-initiating cells (CSC/CIC). These relatively rare cells because of their typical stemness features, are responsible for tumor cell progression and recurrence. Moreover, CSCs have immunomodulatory capabilities and through orchestrating, some immunological profiles can stay safe from host anticancer immunity, and provide immunotherapy resistance in cancer patients. Many studies have shown that CSCs by producing immune system inhibitory factors and interacting with immune checkpoint molecules like CD47,
PDL
-1, CTLA4, Tim3, and
LAG3
, are able to communicate with tumor microenvironment (TME) components and protect cancer cells from immune clearance. In this review, we summarize the CSCs immunological mechanisms and comprehensively discuss interactions between these cells and factors that are present in the TME to repress immune system responses and enhance tumor survival. Therefore, it seems that further studies on this topic will open new doors to improve the therapeutic approaches of malignant cancers.
...
PMID:Immune checkpoints in tumor microenvironment and their relevance to the development of cancer stem cells. 3259 11
