Complement system in cancer: friend or foe of immunotherapy - PubMed
7 hours ago
- #Tumor Microenvironment
- #Complement System
- #Immunotherapy
- The complement system plays a dual role in cancer, influencing both tumor suppression and progression.
- Three activation pathways (classical, alternative, and lectin) initiate immune processes like opsonization and cell lysis.
- Complement activation in the tumor microenvironment can support immune-mediated tumor control or contribute to immune evasion and tumor growth.
- Therapeutic interventions like radiation and certain chemotherapies can trigger complement activation via immunogenic cell death.
- Anaphylatoxins C3a and C5a recruit immune cells but may also foster an immunosuppressive microenvironment.
- Tumor cells upregulate membrane complement regulatory proteins (CD46, CD55, CD59) to escape immune surveillance.
- Complement inhibition, particularly targeting C3aR and C5aR1, synergizes with immune checkpoint inhibitors to enhance tumor rejection.
- Combining complement blockade with proimmunogenic therapies may amplify antitumor effects.
- Strategic modulation of complement could sensitize tumors to immunotherapy and help overcome resistance mechanisms.