|Rhiannon Jenkinson (00:07):
||So people are increasingly looking beyond the adaptive immune system, looking for ways in which they can manipulate the immune response. They're turning now to the innate immune system to look and see whether this can be manipulated to drive antitumor responses. The innate immune system's composed of many different cell types, including NK cells, macrophages, granulocytes. All of these cells could potentially be leveraged to generate an anti-tumor response.
|Rhiannon Jenkinson (00:35):
||So for example, if I elaborate a little bit more on macrophage, these are often present in reasonably large numbers within the tumor micro environment or sat around the margins of the tumor, so these offer a potential therapeutic target for driving antitumor responses. The macrophage typically within the tumor microenvironment have often been subverted, so instead of being pro-inflammatory and driving an anti-tumor response, they're often being subverted into having a phenotype, which enhances the tumor response and also creates a regulated environment in terms of how other immune cell types within the tumor might act.
|Rhiannon Jenkinson (01:15):
||So for example, we know that these cells are producing VEGF, which supports tumor growth, and they're also producing IL-10, which provides a regulated environment for T cell function. So in terms of other functionalities that we can be looking at with macrophage, in these cells we'd normally be expecting them to phagocytose under the right conditions. So if these cells can be driven within the tumor microenvironment to take up tumor cells and phagocytose them and destroy them, and again, this presents a way in which we can drive an anti-tumor response.
|Rhiannon Jenkinson (01:50):
||The tumor associated macrophage phenotype, or TAM, can be modeled in vitro by taking monocytes from healthy donors and then differentiating them under conditions which generates the TAM phenotype so that we can do this and generate cells which are producing VEGF and IL-10. So we recapitulate, to some extent, the cells that are found within the tumor microenvironments.
|Rhiannon Jenkinson (02:14):
||You can then think of a couple of strategies whereby you could come in with your therapeutic to assess whether you can change this phenotype because ultimately the aim would be to switch these cells from that very regulated tumor promoting phenotype to one where you drive sort of a pro-inflammatory microenvironment to cells that are producing for example, IL-6 and TNF alpha.