ACKR4 restrains antitumor immunity by regulating CCL21

Journal: Journal of Experimental Medicine

Published: 2020-06-01

DOI: 10.1084/jem.20190634

Affiliations: 5

Authors: 19

Go to article

Research Highlight

A new target for cancer immunotherapy

: © ROGER HARRIS/SCIENCE PHOTO LIBRARY/Getty Images

: © ROGER HARRIS/SCIENCE PHOTO LIBRARY/Getty Images

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.

Supported content

  1. Journal of Experimental Medicine 217, e20190634 (2020). doi: 10.1084/jem.20190634
Institutions Share
The University of Adelaide (Adelaide Uni), Australia 0.68
QIMR Berghofer Medical Research Institute, Australia 0.21
The University of South Australia (UniSA), Australia 0.05
Women's and Children's Hospital (WCH), SA Health, Australia 0.05

Return