Cancer immunotherapy: Modulating cholesterol metabolism may boost T cells’ killer instincts

A new means of increasing the anticancer activity of immune cells known as killer T cells by modifying cholesterol metabolism is described in a study published in Nature this week.

A subset of T cells, known as CD8+ T cells (killer T cells), are known to infiltrate and attack foreign cells such as tumour cells, and therefore have an important role in antitumour immunity. However, tumours can escape attack through various mechanisms that suppress T-cell activity, so enhancing the activity of CD8+ T cells is of clinical value.

As cholesterol is a component of membrane lipids, which are key regulators of T-cell signalling and function, Chenqi Xu and colleagues investigated whether the antitumour response of CD8+ T cells can be potentiated by modifying cholesterol metabolism. They genetically modified mice so that their T cells lack the enzyme ACAT1 - which generates a form of cholesterol - and find that, in response to the loss of this enzyme, there is an increase in the antitumour activity of CD8+ T cells. They also test the potential of ACAT1 as a drug target for cancer immunotherapy by treating small numbers of mice across several experiments with avasimibe, an ACAT1 inhibitor, and find that tumour growth was inhibited and survival time prolonged.

The authors suggest that this new mechanism could be used to complement other current therapies, such as immune checkpoint blockade.

doi: 10.1038/nature17412

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