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The Tumor Microenvironment02:17

The Tumor Microenvironment

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Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
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Autocrine Signaling01:01

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Autocrine signaling is one of the many signaling mechanisms that function inside multicellular organisms to carry out intercellular communication. In this type of signaling mechanism, the same cell that secretes an extracellular signaling molecule also expresses the receptors to bind and respond to that signaling molecule.
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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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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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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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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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IL-1 Signaling in Tumor Microenvironment.

Weizhou Zhang1, Nicholas Borcherding2, Ryan Kolb3

  • 1Department of Pathology, Immunology and Laboratory Medicine, UF Health Cancer Center, University of Florida, Gainesville, FL, USA. zhangw@ufl.edu.

Advances in Experimental Medicine and Biology
|February 16, 2020
PubMed
Summary

Interleukin 1 (IL-1) signaling, involving IL-1 and its receptor IL-1R1, plays complex roles in cancer. Targeting this pathway offers potential for novel cancer therapies by modulating the tumor microenvironment.

Keywords:
Breast cancerCancer progressionCancer therapyColorectal cancerHepatocellular carcinomaIL-1 signaling pathwayIL-1R1IL-1RAInterleukin-1αInterleukin-1βMelanomaMouse modelsPleiotropic effectsSarcomaTumor microenvironment

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Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Interleukin 1 (IL-1) is a key cytokine influencing inflammation with diverse roles in cancer development.
  • IL-1α and IL-1β are major forms, binding to the IL-1 receptor 1 (IL-1R1) expressed on various cell types.
  • IL-1 signaling activates pathways like NF-kB and MAP kinase, impacting tumor progression.

Purpose of the Study:

  • To elucidate the multifaceted role of IL-1/IL-1R1 signaling in different cell types within the tumor microenvironment.
  • To explore the therapeutic potential of targeting the IL-1/IL-1R1 pathway in cancer treatment.

Main Methods:

  • Utilizing IL-1R1 conditional knockout mouse models to dissect cell-type-specific functions.
  • Analyzing the impact of IL-1/IL-1R1 signaling on various cellular components of the tumor microenvironment.

Main Results:

  • IL-1/IL-1R1 signaling exhibits context-dependent and sometimes opposing effects on tumor development.
  • The expression of IL-1R1 across diverse cell types dictates the specific roles of IL-1 signaling in cancer.

Conclusions:

  • IL-1/IL-1R1 signaling is a critical regulator of the tumor microenvironment with complex roles in cancer.
  • Targeting the IL-1/IL-1R1 pathway presents a promising strategy for developing new cancer therapies.