Melody Swartz: Flow in the tumour microenvironment

Flow in the tumour microenvironment: Linking mechanobiology with immunology.

Tumours often engage the lymphatic system to invade and metastasize. The tumour-draining lymph node (dLN) may be an immune privileged site that protects the tumour from host immunity, and lymph flow draining tumours is often increased, enhancing communication between the tumour and the sentinel node. In addition to increasing transport of tumour antigens and regulatory cytokines to the lymph node, increased lymph flow in the tumour margin causes mechanical stress-induced changes in stromal cells that stiffen the matrix and alter the immune microenvironment of the tumour.In this proposed project, we will investigate the interplay between lymphatic drainage and flow-induced mechanotransduction in the tumour stroma that may synergize to promote tumour immune escape by appropriating lymphatic mechanisms of peripheral tolerance. We will address the hypothesis that lymphatic drainage and flow-induced mechanotransduction in the tumour stroma synergistically promote tumour immune escape by altering the immune microenvironment, and that targeting lymphatic drainage from the tumour may represent a new avenue for tumour immunotherapy. For the latter, we will develop strategies to limit or block lymphatic flow in the tumour microenvironment and characterize their ability to improve the efficacy of tumour immunotherapy by dampening local immunosuppression in the tumour stroma and tumour-draining lymph node (dLN). We will combine in vivo mouse models and intravital imaging with engineered in vitro microenvironments and nanoparticle-based targeting strategies in three broad aims designed to constitute several PhD and postdoctoral projects.

Max ERC funding: 2.5 million Euros
Duration: 60 months
Host institution: EPFL
Project acronym: LYMPHIMMUNE
Domain: Life sciences