Local and Cell-intrinsic complement: The new player in cancer progression

Area of Science:

• Immunology
• Oncology

Background:

• The complement system is a critical part of innate immunity.
• Traditionally, its role in cancer was viewed as extracellular, with dual functions as a tumor suppressor and promoter.
• Emerging evidence points to non-canonical, intracellular roles in tumor progression.

Purpose of the Study:

• To explore the paradoxical roles of the complement system in cancer.
• To highlight recent discoveries on intracellular complement functions.
• To discuss challenges and future directions in understanding complement's role in oncology.

Main Methods:

• Review of recent scientific literature.
• Analysis of gene expression data (acknowledged limitations).
• Discussion of emerging technologies like gene editing and single-cell analysis.

Main Results:

• Complement system exhibits both tumor-suppressive and tumor-promoting activities.
• Intracellular complement activation influences tumor proliferation, immune evasion, and metastasis.
• Tumors utilize complement for immunosuppression and resistance to therapy.
• The concept of an intracellular complement system ('complosome') suggests roles in metabolism and stress responses.

Conclusions:

• Complement's role in cancer is complex, extending beyond extracellular functions.
• Understanding intracellular complement signaling is crucial for cancer research.
• Further research using advanced technologies is needed to develop novel cancer therapies targeting the complement system.