Tumor-Induced Disruption of Proximal TCR-Mediated Signal Transduction in Tumor-Infiltrating CD8+ Lymphocytes Inactivates Antitumor Effector Phase.
Summary of "Tumor-Induced Disruption of Proximal TCR-Mediated Signal Transduction in Tumor-Infiltrating CD8+ Lymphocytes Inactivates Antitumor Effector Phase."
The presence in cancer tissue of Ag-specific, activated tumor infiltrating CD8(+) T cells proves that tumors express Ags capable of eliciting immune response. Therefore, in general, tumor escape from immune-mediated clearance is not attributable to immunological ignorance. However, tumor-infiltrating lymphocytes are defective in effector phase function, demonstrating tumor-induced immune suppression that likely underlies tumor escape. Since exocytosis of lytic granules is dependent upon TCR-mediated signal transduction, it is a reasonable contention that tumors may induce defective signal transduction in tumor infiltrating T cells. In this review, we consider the biochemical basis for antitumor T cell dysfunction, focusing on the role of inhibitory signaling receptors in restricting TCR-mediated signaling in tumor-infiltrating lymphocytes.
Department of Cell Biology.
This article was published in the following journal.
Name: Journal of immunology (Baltimore, Md. : 1950)
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21127315
- DOI: http://dx.doi.org/10.4049/jimmunol.1001157
Medical and Biotech [MESH] Definitions
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activa
Suppressor Of Cytokine Signaling Proteins
A family of structurally related proteins that are induced by CYTOKINES and negatively regulate cytokine-mediated SIGNAL TRANSDUCTION PATHWAYS. SOCS proteins contain a central SH2 DOMAIN and a C-terminal region of homology known as the SOCS box.
Tumor Necrosis Factors
A family of proteins that were originally identified by their ability to cause NECROSIS of NEOPLASMS. Their necrotic effect on cells is mediated through TUMOR NECROSIS FACTOR RECEPTORS which induce APOPTOSIS.
Protein Inhibitors Of Activated Stat
A family of structurally related proteins that are constitutively expressed and that negatively regulate cytokine-mediated SIGNAL TRANSDUCTION PATHWAYS. PIAS proteins inhibit the activity of signal transducers and activators of transcription.
Endodermal Sinus Tumor
An unusual and aggressive tumor of germ-cell origin that reproduces the extraembryonic structures of the early embryo. It is the most common malignant germ cell tumor found in children. It is characterized by a labyrinthine glandular pattern of flat epithelial cells and rounded papillary processes with a central capillary (Schiller-Duval body). The tumor is rarely bilateral. Before the use of combination chemotherapy, the tumor was almost invariably fatal. (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1189)
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