Role of monocytes in cancer progression (an in vitro approach)

Macrophages, predominantly derived from highly plastic circulating monocytes, constitute one of the first line of defense against exogenous and endogenous threats. The tumor microenvironment (TME), comprising cellular and acellular components, plays synergistic roles in cancer progression. Tumor associated macrophages (TAMs) are key cellular components of the TME and adopt differential phenotypes such as M1-like pro-inflammatory and M2-like pro-tumorigenic upon classical polarization processes. In this work I studied in vitro the effect of M1/M2-like TAMs on functional characteristics of cancer cells such as proliferation and invasion of neighboring tissues and chimeric antigen receptor (CAR) T cell immunotherapy response. Using different cancer cell models (ovarian, melanoma, gastric and 3 different patient-derived glioblastoma cells) and different healthy donors of peripheral blood mononuclear cells (PBMCs) in monocultures (cancer cells) and co-cultures (cancer cells and M1/M2-like macrophages), my results show a substantially reduced cancer cell growth in M1-like co-cultures in all models tested. Glioblastoma (GBM) cells co-cultured in three-dimensional co-cultures with M1-like macrophages displayed an impaired ability to spread/invade. Moreover, CAR T cells against the tumor associated antigen IL13RA2 produced an impaired anti-tumor response toward GBM cells when co-cultured with M2-like macrophages.