UNRAVELLING THE CANCER-ASSOCIATED ROLE OF MONOCYTES AND MACROPHAGES USING 3D MICROFLUIDIC MODELS

Abstract

Monocytes (Mos) and macrophages (Macs) are immune cells that support tumour progression through their response to biological and mechanical factors in the tumour microenvironment (TME). The TME also shapes the roles of these cells. Understanding the roles of Mos/Macs in the TME is thus crucial for improved immunotherapy. Murine models have been useful to understand Mo/Mac biology, but are costly, ethically contentious, and cannot fully represent human settings. There is a need for improved in vitro human-relevant TME models for immuno-oncology studies. My dissertation demonstrates the development of 3D human TME microfluidic models to contribute insight into the cancer-associated roles of Mos/Macs, including Mo suppression of engineered T cells by immune checkpoint signalling and Mac migration in response to tumour interstitial flow and cytokines. It also demonstrates the potential for an in vitro vascularised TME setting to be achieved to evaluate the ability of Mo/Mac-modulating nanoparticles to regulate Mo/Mac activities.