MAR 20, 2018 05:50 PM PDT

You better not get a viral infection if you have cancer!

In a newly published paper, scientists provide evidence that cancer secretes micro-particles (exosomes) which dampens immune response to viral infection.

Roles of exosomes in cancer;  Courtesy: Zhang, X., Yuan, X., Shi, H. et al. J Hematol Oncol (2015) 8: 83

The immune system recognizes different molecules on viral particles through series of pathogen-associated molecular pattern recognition sequences (PAMPS) expressing on various innate immune cells. These cells initiate a series of signaling upon activation of PAMPS after binding with viral particles. Activation ultimately leads to the production of the potent antiviral molecules, type I interferons, and various inflammatory cytokines providing an excellent immune response to viral infection. Modulation of the immune response can be caused by specific disease and condition such as malignancy of cancer, transplantation, infection, chemotherapy, systemic vasculitis and connective tissue disease. These modulations can have far-reaching repercussion on the outcome of infection and may leave humans susceptible to pathogens.

It is a well-known fact that cancer reduces the immune response in its microenvironment to escape antitumor activity. Recent studies even provided evidence that tumor cells secrete immunomodulatory molecules within exosomes (membrane-enclosed small vesicles). These exosomes are called tumor-derived exosomes (TEX) and can be transferred horizontally across the body to carry functional biomolecules such as proteins, lipids, DNA and RNA. TEX has been shown to be the regulator of tumorigenesis and impart the indirect effect on the immune system to provide tumor growth and metastasis. However, TEX effect on viral immune response has not been shown until now. The team provides that data for the first time that TEX can carry a biomolecule to macrophages to reduce its ability to produce type I interferon, an essential protein in antivirus immune response.

In this study, authors first found a clinical relevant data where lung cancer patients had a lower level of serum interferon-beta in response to flu infection than people without cancer. To investigate further, authors conducted series of in-vitro and in-vivo experiments in animal models to delineate the relevance and mechanism of this clinical finding further. They found that TEX produced by cancer cells contained a protein, epidermal growth factor receptor (EGFR), which could be transferred to innate immune cells such as macrophages. These macrophages could not produce enough type I interferon in response to virus infection upon encountering EGFR loaded exosomes. Scientists further wanted to know how EGFR exposure in macrophages leads to reduced anti-viral protein. They found that EGFR induced expression of MEKK2, a type of kinase protein, which ultimately caused deregulation of interferon production. The mechanism by which MEKK2 imparts this effect in macrophages was further investigated and found to induce phosphorylation of a transcription factor IRF-3 at a serine173 position in MEKK2 dependent manner. IRF-3 is a critical transcription factor for production of type-I interferon, once activated it localizes into the nucleus of the cells, where it binds to the DNA of interferon gene and thus leading to its production. MEKK3 induced IRF-3 phosphorylation led to k33 linked poly-ubiquitination at a specific site of IRF-3 causing interference in its translocation into the nucleus of the cells and thus resulting in reduced expression of interferon genes.

Note: Exosome in cancer; Courtsey: Thermo Fisher Scientific 

Many recent studies have shown that exosomes produced by tumors can modulate the immune response to give cancer cells a survival, propagation and metastatic advantage. However, this is the first time; a detailed mechanistic study provides evidence for reduced antiviral immune response among cancer patients.

About the Author
  • Biological research scientist by profession with passion to write about science in general.
You May Also Like
AUG 28, 2018
Drug Discovery
AUG 28, 2018
Combination Therapy for Advanced Melonoma
According to a research study led by UCLA, a bacteria-like agent used in combination with an immunotherapeutic drug may help patients survive longer with a...
SEP 15, 2018
Clinical & Molecular DX
SEP 15, 2018
Cancer & Anoikis: A Match Not Made in Heaven
Anoikis have always been intimately entwined with cancer, henceforth the quest to seek how they came to be as such....
SEP 20, 2018
Genetics & Genomics
SEP 20, 2018
Liquid Phase Separation may Play a Role in Cancer
Not all liquids mix, like oil and water; the phenomenon is called liquid-liquid phase separation. We're learning more about its role in cells....
SEP 26, 2018
Videos
SEP 26, 2018
Cancer Immunotherapy
Video illustration about how tumor cells are sensed and destroyed by the immune system and how tumors evolve and detect immune-mediated eliminations, as well as iimmunotherapies associated....
NOV 12, 2018
Health & Medicine
NOV 12, 2018
Researchers find that obesity has a paradoxical effect on Cancer
Cancer therapy works differently in different people. Understanding what effects the individual body's response to treatment will be crucial for the development...
NOV 20, 2018
Immunology
NOV 20, 2018
Mutations Mutations Which Ones Do We Want?
A team at UCSF makes use of new SLICE tool to generate mutations that reveal specific genetic functions....
Loading Comments...