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mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

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The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
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The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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Related Experiment Video

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Adenoviral Transduction of Naive CD4 T Cells to Study Treg Differentiation
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mTOR signaling, Tregs and immune modulation.

Nicole M Chapman1, Hongbo Chi

  • 1Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.

Immunotherapy
|December 20, 2014
PubMed
Summary

Regulatory T cells (Tregs) control immune tolerance. Targeting mTOR signaling in Tregs offers therapeutic potential, but its effects vary across diseases, requiring careful consideration for optimal treatment strategies.

Keywords:
T cellsimmunotherapymTORC1rapamycinregulatory T cells

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Area of Science:

  • Immunology
  • Cellular Biology
  • Molecular Medicine

Background:

  • Foxp3(+) regulatory T cells (Tregs) are crucial for immune tolerance.
  • Dysregulated Treg function is implicated in various disease pathologies.
  • The mechanistic target of rapamycin (mTOR) pathway is a key regulator of T cell function.

Purpose of the Study:

  • To summarize Treg-mediated immune suppression and their role in disease.
  • To review therapeutic strategies for modulating Treg function.
  • To discuss the impact of mTOR inhibition on T cells and Tregs.

Main Methods:

  • Literature review of Treg function and mTOR signaling.
  • Analysis of existing studies on mTOR inhibitors in T cell biology.
  • Synthesis of data on therapeutic targeting of Tregs via mTOR.

Main Results:

  • mTOR signaling critically influences Treg differentiation, homeostasis, and function.
  • mTOR inhibition has diverse effects on both conventional T cells and Tregs.
  • The therapeutic benefit of modulating Treg mTOR activity is context-dependent.

Conclusions:

  • Targeting mTOR in Tregs presents a potential therapeutic avenue for immune-related diseases.
  • The specific effects of mTOR inhibition on Tregs can be beneficial or detrimental depending on the disease context.
  • Further research is needed to optimize mTOR-targeted Treg therapies.