Complement anaphylatoxins as immune regulators in cancer

Area of Science:

• Immunology
• Oncology
• Complement System Biology

Background:

• The complement system is crucial for innate immunity.
• Emerging research suggests complement anaphylatoxins C3a and C5a promote tumor growth and progression.
• Tumors can produce C3a and C5a, implicating complement in fostering cancer rather than defending against it.

Purpose of the Study:

• To systematically review literature on complement anaphylatoxins' effects on immune cells within the tumor microenvironment.
• To explore the paradigm of complement as a regulator of antitumor immunity.
• To understand how complement signaling influences tumor progression.

Main Methods:

• Systematic literature review.
• Identification and analysis of studies investigating complement anaphylatoxins (C3a, C5a) and their receptors (C3aR, C5aR) on immune cells.
• Focus on studies involving cancer models (lymphoma, ovarian, cervical, lung, breast, mammary).

Main Results:

• Six studies were identified across various cancer models.
• Evidence suggests complement anaphylatoxins modulate immune cell function within the tumor microenvironment.
• Complement-mediated suppression of immune effector cells is a putative mechanism for promoting tumor growth.

Conclusions:

• The complement system, particularly anaphylatoxins C3a and C5a, plays a significant role in regulating the immune response within the tumor microenvironment.
• Complement signaling can impair antitumor immunity, contributing to cancer progression.
• This supports a paradigm shift in understanding complement's role in cancer, moving from defense to potential promotion.