Abstract 414: Suppressive bioassays using macrophages and MDSCs

Abstract

Abstract The increasing interest in the tumour microenvironment leads to focus on new bioassays to represent all the players of the cancer immune response. Some of these players like Tumour Associated Macrophages (TAM) and Myeloid Derived Suppressor Cells (MDSC) play an important role by downregulating the anti-tumour response. Their regulation mechanisms constitute an important target for new therapeutics. In order to study these mechanisms in a human model, suppressive bioassays, mimicking the suppressive action of these cells on T cells activations, were developed. One of the important players in the tumor microenvironment are the macrophages which possess important active and regulatory functions in both innate and adaptive immune responses. Classical activated macrophages, also classified as M1-like macrophages, comprise immune effector cells with an acute inflammatory phenotype while the alternatively activated M2-like macrophages have suppressive and healing capacities. Tumor associated macrophages (TAMs) are present at high densities in solid tumors and share many characteristics with so called M2 macrophages. Although distinguished classification and in vitro generation and polarization of M1- and M2-like macrophages is challenging, in vitro assays can be a first step to screen the effect of the test molecules on the phenotype and function of the macrophages. For example, macrophage precursors display extraordinary plasticity in response to exogenous and endogenous stimuli which can lead them to M2-polarized macrophages or towards the M1-activated status. Using in vitro polarization and functional macrophage assays, one can screen molecules with the potential to influence M1 and M2 like macrophage generation and polarization. Next to that, the effect of the test molecules on the function of the macrophages can be evaluated using a macrophage suppressive assay. Here the ability of the molecules to reverse the stimulating effect of the M1-macropahges or suppressive effect of the M2-macrophages on T cells can be determined by measuring their proliferation and cytokine production. Myeloid-derived suppressor cells (MDSC) can also be found in the tumour microenvironment and present a highly suppressive phenotype. Their role in relation to cancer development and progression has shown to be of great importance. Therefore, the ability of molecules to reverse the suppressive function of the MDSC can be evaluated in vitro using these cell-type specific suppressive bioassays. The use of the bioassays contributes to a better understanding of the tumour microenvironment and the steps needed to generate an anti-tumour response by the immune system will help to assess the functional potential of new drugs, design clinical trials and ultimately discover relevant biomarkers. Citation Format: Amin Osmani, Thibaut Janss, Thibault Jonckheere, Séverine Giltaire, Sofie Pattijn, Jana Schockaert. Suppressive bioassays using macrophages and MDSCs [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 414.