Targeting the microenvironment
Aggressive lymphomas often contain large numbers of dying tumour cells alongside those that proliferate. In order for a cancer to grow, this cell-birth/cell-death equation must favour cell birth. Contrary to expectation, we have found that dying tumour cells produce factors that ‘seed the soil’ to help their viable, growing counterparts. They achieve this by a variety of mechanisms, including (1) production of biologically active molecules encapsulated in tiny, membrane-bound bubbles that are released from the dying lymphoma cells and (2) through activation of normal professional “eating-cells” known as phagocytes that reside in the tumour niche, engulfing and digesting the dying tumour cells in their neighbourhood. In this programme, we aim to understand how the dying cells promote tumour growth by identifying the active components of the ‘micro-bubbles’ they release and how the dying cells and micro-bubbles activate the neighbouring phagocytes. Ultimately, by targeting the underlying mechanisms, we aim to switch the cell-birth/cell-death equation in favour of net cell death, thereby driving cancer cure.