Properdin Is a Modulator of Tumour Immunity in a Syngeneic Mouse Melanoma Model

Area of Science:

• Immunology
• Oncology
• Innate Immunity

Background:

• Tumours often exhibit low immunogenicity, complicating immune-mediated control.
• The role of the complement system in tumour immunity is under investigation, with conflicting reports.
• Properdin, a complement activator, has been suggested to play a role in tumour progression.

Purpose of the Study:

• To investigate the role of properdin in modulating the tumour microenvironment and immune cell populations during melanoma development.
• To assess the impact of properdin deficiency on myeloid-derived suppressor cells (MDSCs) and M2 macrophages in a B16F10 melanoma model.

Main Methods:

• Properdin-deficient and wildtype mice were subcutaneously injected with B16F10 melanoma cells.
• Tumour growth, chemokine profiles, and immune cell frequencies (MDSCs, M2 macrophages) were analyzed.
• Serum levels of complement components (C5a, sC5b-9) and CCL2 were quantified.

Main Results:

• No significant difference in tumour growth was observed between properdin-deficient and wildtype mice.
• Properdin-deficient mice exhibited significantly reduced frequencies of MDSCs in tumours and spleens.
• Decreased splenic M2 macrophages and reduced serum levels of C5a, sC5b-9, and CCL2 were noted in properdin-deficient mice.

Conclusions:

• Intact complement amplification, involving properdin, supports a tumour microenvironment that may suppress anti-tumour immune responses.
• Properdin deficiency leads to a reduction in immunosuppressive cell populations, suggesting a potential therapeutic target.