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Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

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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 Tumor Microenvironment02:17

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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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Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
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Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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Combining microenvironment normalization strategies to improve cancer immunotherapy.

Fotios Mpekris1, Chrysovalantis Voutouri1, James W Baish2

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Optimizing cancer immunotherapy requires normalizing the tumor microenvironment (TME). Sequential low-dose antiangiogenic therapy combined with immunotherapy improves outcomes by enhancing tumor perfusion, a potential biomarker for treatment response.

Keywords:
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Area of Science:

  • Oncology
  • Immunology
  • Biomedical Engineering

Background:

  • Immunotherapy has transformed cancer treatment but is limited by poor tumor perfusion and hypoxia within the tumor microenvironment (TME).
  • Hypoxia in the TME suppresses immune responses, hindering the effectiveness of cancer immunotherapies.
  • Antiangiogenic drugs and mechanotherapeutics are explored to normalize the TME and improve therapeutic delivery.

Purpose of the Study:

  • To develop a mathematical framework modeling the TME to identify strategies for enhancing cancer immunotherapy efficacy.
  • To investigate the combined effects of immunotherapy and TME normalization strategies, including antiangiogenic treatments.
  • To determine the role of vascular normalization and stroma normalization in improving immunotherapy outcomes.

Main Methods:

  • Development of a mathematical model integrating cancer cells, immune cells, stroma, angiogenic molecules, and vasculature.
  • Comparison of model predictions with data from five experimental studies.
  • Simulation of various treatment strategies, including sequential and concurrent administration of immunotherapy and antiangiogenic agents.

Main Results:

  • Low-dose antiangiogenic treatment, when sequentially administered with immunotherapy, enhances treatment efficacy.
  • High-dose antiangiogenic treatment reduces efficacy due to excessive vessel pruning and increased hypoxia.
  • Stroma normalization provides additive benefits to immunotherapy, further increasing efficacy.

Conclusions:

  • Vessel functionality is a critical determinant of immunotherapy efficacy.
  • Increased tumor perfusion should be investigated as a predictive biomarker for response to cancer immunotherapy.
  • Optimizing TME normalization strategies, particularly vascular normalization, is key to improving immunotherapy outcomes.