Oxygen Starved Cancer Cells Recruit Immune Cells to Survive
Pancreatic cancer cells can recruit immune cells to restore their oxygen supply in response to anti-angiogenesis therapies.
To maintain their nutrient and oxygen supplies tumour cells initiate the formation of new blood vessels, in a process known as angiogenesis. Many cancer therapies work by blocking angiogenesis, as the process does not usually occur in healthy tissues. This causes the cancer cells to die from a lack of oxygen.
However, many patients who receive anti-angiogenesis drugs experience cancer remission after only 1-2 months. As it appeared that the tumour cells had evolved resistance to the drug by finding a new way to obtain oxygen, this study investigated how the cancer cells were able to survive oxygen cut-off.
Cancer cells respond to oxygen by upregulating the 1α HIF1A transcription factor, which initiates angiogenesis. The oxygen sensing protein HF1 was blocked in mice models of pancreatic tumours, which would ordinarily kill the tumours from lack of oxygen. However, after a month the tumour cells started to grow again, indicating that they had found a new oxygen supply.
It was found that the cancer cells evolved to inhibit the breakdown of glycogen, causing a build-up of the sugar within the cell. This initiated the production of inflammatory interleukins that drew immune cells into the tumour microenvironment. The immune cells then create new blood vessels that can also supply the cancer cells with oxygen.
By finding a way to block this process, a new therapy to keep anti-angiogenesis drugs working could be developed.