Complement-Dependent Cytotoxicity

Definition

Complement-dependent cytotoxicity (CDC) is a mechanism by which the complement system, a part of the immune system, can directly lyse or kill target cells. This process involves the activation of the complement cascade, leading to the formation of a membrane attack complex that disrupts the target cell's membrane and causes cell death.

5 Must Know Facts For Your Next Test

1. Complement-dependent cytotoxicity is an important mechanism for the immune system to directly kill tumor cells and pathogens.
2. The complement cascade is initiated when antibodies bind to the target cell surface, triggering the activation of the classical complement pathway.
3. Activation of the complement cascade leads to the formation of the membrane attack complex, which inserts into the target cell's membrane and causes osmotic lysis.
4. Complement-dependent cytotoxicity is a key mechanism of action for some cancer immunotherapies, such as monoclonal antibodies that target tumor-associated antigens.
5. Evasion of complement-dependent cytotoxicity is a common immune escape mechanism employed by cancer cells, and understanding this process is crucial for developing more effective immunotherapies.

Review Questions

• Explain the role of the complement system in complement-dependent cytotoxicity and how it contributes to the immune response against cancer.
  • The complement system is a critical component of the innate immune response, and its activation is a key mechanism by which the immune system can directly lyse or kill target cells, including cancer cells. In complement-dependent cytotoxicity, the binding of antibodies to tumor-associated antigens on the surface of cancer cells triggers the activation of the classical complement pathway. This leads to the sequential activation of complement proteins and the formation of the membrane attack complex, which inserts into the target cell's membrane and causes osmotic lysis and cell death. By directly killing cancer cells, complement-dependent cytotoxicity is an important effector function that contributes to the immune system's ability to recognize and eliminate tumors.
• Describe how cancer cells can evade complement-dependent cytotoxicity and the implications for cancer immunotherapy development.
  • Cancer cells have developed various mechanisms to evade complement-dependent cytotoxicity, which can limit the effectiveness of this immune defense pathway. Some of these evasion strategies include: 1) Downregulation or masking of tumor-associated antigens to prevent antibody binding, 2) Upregulation of complement regulatory proteins that inhibit the complement cascade, and 3) Activation of signaling pathways that promote the survival and proliferation of cancer cells in the face of complement attack. Understanding these evasion mechanisms is crucial for the development of more effective cancer immunotherapies, as therapies that can overcome complement evasion or enhance complement-dependent cytotoxicity may be more successful in eliciting a robust anti-tumor immune response.
• Analyze the potential therapeutic applications of harnessing complement-dependent cytotoxicity in the context of cancer immunobiology and immunotherapy.
  • Complement-dependent cytotoxicity has significant therapeutic potential in the field of cancer immunobiology and immunotherapy. By targeting tumor-associated antigens with monoclonal antibodies, it is possible to activate the complement cascade and induce the direct lysis of cancer cells. This mechanism of action is already being exploited in the development of several FDA-approved cancer immunotherapies, such as rituximab and ofatumumab, which target CD20 on B-cell malignancies. Additionally, ongoing research is exploring ways to further enhance complement-dependent cytotoxicity, such as by modulating complement regulatory proteins or engineering antibodies with improved complement-activating properties. As our understanding of the complex interplay between cancer cells and the complement system continues to evolve, the therapeutic targeting of complement-dependent cytotoxicity is likely to become an increasingly important strategy in the fight against cancer.

Related terms

Complement System:

The complement system is a collection of proteins that work together as part of the immune response to help or 'complement' the ability of antibodies and phagocytic cells to clear pathogens and damaged cells from an organism.

Membrane Attack Complex (MAC): The membrane attack complex is the final step in the complement cascade, where the complement proteins assemble into a pore-forming structure that inserts into the target cell's membrane, causing it to rupture and the cell to lyse.

Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC): ADCC is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell, whose membrane-surface antigens have been bound by specific antibodies.