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

Izzat A M Al-Rayahi,Cordula M Stover,Lee R Machado

doi:10.3390/medicina57020085

Izzat A M Al-Rayahi, Cordula M Stover + Show 1 more

Open Access

https://doi.org/10.3390/medicina57020085

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Abstract

Background and Objectives: Tumours are often low immunogenic. The role of complement, an innate immune defence system, in tumour control has begun to be elucidated, but findings are conflicting. A role for properdin, an amplifier of complement activation, in tumour control has recently been implicated. Materials and Methods: Properdin-deficient and congenic wildtype mice were injected subcutaneously with B16F10 melanoma cells. Tumour mass and chemokine profile were assessed. The frequencies of CD45+CD11b+ Gr-1+ cells were determined from tumours and spleens, and CD206+ F4/80+ cells were evaluated in spleens. Sera were analysed for C5a, sC5b-9, and CCL2. Results: Whilst there was no difference in tumour growth at study endpoint, properdin-deficient mice had significantly fewer myeloid-derived suppressor cells (MDSCs) in their tumours and spleens. Splenic M2 type macrophages and serum levels of C5a, sC5b-9, and CCL2 were decreased in properdin-deficient compared to wildtype mice. Conclusions: The presence of intact complement amplification sustains an environment that lessens potential anti-tumour responses.

Highlights

Mouse models of various tumours have been employed as preclinical models to inform or direct management of human disease, though they have their limitations [1]
We have previously studied the in vitro effect of B16F10 conditioned medium on the profile of bone marrow-derived macrophages of properdin-deficient and wildtype mice
We found that while overall tumour growth was not significantly impacted by the absence of properdin, there was significantly less CCL2 chemokine and fewer Gr1+ CD11b+ myeloid-derived suppressor cells (MDSCs) as well as M2 type macrophages compared with wildtype counterparts

Summary

Introduction

Mouse models of various tumours have been employed as preclinical models to inform or direct management of human disease, though they have their limitations [1]. Immune suppressive cell populations (regulatory T cells and myeloid-derived suppressor cells (MDSCs)) are detectable in tumour as well as spleen and associate with a poor response to experimental immunotherapy [4]. Monocytic replenishment from spleen in a mouse model of lung adenocarcinoma was CCR2 dependent and impacted on tumour growth [7]. A role for properdin, an amplifier of complement activation, in tumour control has recently been implicated. Materials and Methods: Properdin-deficient and congenic wildtype mice were injected subcutaneously with B16F10 melanoma cells. Results: Whilst there was no difference in tumour growth at study endpoint, properdin-deficient mice had significantly fewer myeloid-derived suppressor cells (MDSCs) in their tumours and spleens. Splenic M2 type macrophages and serum levels of C5a, sC5b-9, and CCL2 were decreased in properdin-deficient compared to wildtype mice. Conclusions: The presence of intact complement amplification sustains an environment that lessens potential anti-tumour responses

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