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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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Tumor Immunotherapy01:27

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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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Tumor Progression02:07

Tumor Progression

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Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
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Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
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Loss of Tumor Suppressor Gene Functions01:12

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Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
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Oncolytic Virotherapy and the Tumor Microenvironment.

Sara E Berkey1, Steve H Thorne2,3, David L Bartlett2

  • 1Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA. berkeyse@upmc.edu.

Advances in Experimental Medicine and Biology
|December 25, 2017
PubMed
Summary

Oncolytic viral therapy uses genetically modified viruses to target and destroy cancer cells. These "armed" viruses enhance immune response and disrupt tumor growth, offering a promising new cancer treatment.

Keywords:
Cytokine expressionExtracellular matrixImmune activationOncolytic virusVascular inhibition

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Area of Science:

  • Oncology
  • Virology
  • Immunotherapy

Background:

  • Oncolytic viral therapy is an emerging cancer treatment strategy.
  • Genetically modified viruses show promise for treating various cancers, including breast, colorectal, hepatocellular, and melanoma.

Purpose of the Study:

  • To explore the mechanisms and potential of targeted and armed oncolytic viruses in cancer therapy.
  • To highlight how these viruses can be engineered to selectively kill cancer cells and modify the tumor microenvironment.

Main Methods:

  • Genetic modification of viruses to achieve selective replication in cancer cells.
  • Engineering viruses to express transgenes that inhibit tumor progression and modulate the immune system.
  • Investigating the virus's ability to induce anti-vascular effects and disrupt the extracellular matrix.

Main Results:

  • Engineered oncolytic viruses selectively replicate within cancer cells, leading to tumor cell death.
  • Transgene products from armed viruses induce cell death, reduce viral virulence, and compromise tumor vascularity.
  • Oncolytic viruses enhance immune responses through cytokines and chemokines, improve tumor cell death, and disrupt the tumor microenvironment.

Conclusions:

  • Targeted and armed oncolytic viruses represent a potent therapeutic strategy for multiple malignancies.
  • These viruses offer a multi-pronged approach by directly killing cancer cells, enhancing anti-tumor immunity, and disrupting the tumor's supportive environment.
  • Further development of oncolytic viral therapy holds significant promise for improving cancer treatment outcomes.