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Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

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.
Complement System01:27

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The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a membrane...
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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Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
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Antimicrobial proteins are important components of the immune system. They aid the body in combating pathogens by either killing them directly or hindering their replication processes. Four main types of antimicrobial substances are interferons, the complement system, iron-binding proteins, and antimicrobial proteins.
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Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...

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In Vitro Methods for Comparing Target Binding and CDC Induction Between Therapeutic Antibodies: Applications in Biosimilarity Analysis
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Modulation of the antitumor immune response by complement.

Maciej M Markiewski1, Robert A DeAngelis, Fabian Benencia

  • 1Department of Pathology and Laboratory Medicine, Medical School of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

Nature Immunology
|September 30, 2008
PubMed
Summary

Complement C5a promotes tumor growth by suppressing CD8(+) T cells. Inhibiting C5a signaling or myeloid-derived suppressor cells offers a novel cancer therapy strategy.

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Area of Science:

  • Immunology
  • Oncology
  • Complement System

Background:

  • The role of complement activation products in tumor progression is largely unexplored.
  • Tumor microenvironments can evade immune surveillance through various mechanisms.

Purpose of the Study:

  • To investigate the role of complement C5a in tumor growth.
  • To determine the impact of C5a on antitumor immune responses.
  • To explore complement inhibition as a cancer treatment strategy.

Main Methods:

  • Analysis of complement C5a generation within the tumor microenvironment.
  • Assessment of CD8(+) T cell function in the presence of C5a.
  • Evaluation of myeloid-derived suppressor cell recruitment and function.
  • Pharmacological blockade of the C5a receptor.

Main Results:

  • Complement C5a generation in tumors enhances tumor growth.
  • C5a suppresses antitumor CD8(+) T cell responses.
  • C5a promotes the recruitment and enhances the suppressive capacity of myeloid-derived suppressor cells.
  • C5a-mediated suppression involves reactive oxygen and nitrogen species.
  • Blocking the C5a receptor significantly inhibits tumor growth, comparable to paclitaxel.

Conclusions:

  • Complement C5a plays a critical role in promoting tumor growth by inhibiting anti-tumor immunity.
  • Targeting the C5a pathway, including myeloid-derived suppressor cells, represents a promising therapeutic approach for cancer treatment.