ACKR4 restrains antitumor immunity by regulating CCL21

A new target for cancer immunotherapy

31 May 2021

A protein that regulates levels of immune signalling molecules in the tumour surroundings offers a new target for anti-cancer immunotherapy.

Despite showing immense clinical promise, cancer drugs that promote the activity of ‘killer’ T cells have limited efficacy against some tumours in which the immune cells seem to be kept at bay by some kind of molecular signal.

Now, a University of Adelaide-team has identified that signal as atypical chemokine receptor 4 (ACKR4).

In the tumour microenvironment, this receptor protein shapes the abundance and distribution of a signalling molecule called CCL21, which in turn affects the retention of dendritic cells, a type of immune cell that regulates the responsiveness of cancer-killing T cells.

In the absence of ACKR4, killer T cells flood into tumours, inhibiting their growth.

Drugs that block ACKR4 — or, alternatively, boost levels of CCL21 — could thus work in tandem with other cancer immunotherapies to supercharge T cell activity.

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References

1. Journal of Experimental Medicine 217, e20190634 (2020). doi: 10.1084/jem.20190634