Interference identifies immune modulators

Abstract

A broad in vivo screen of the effects of specific gene inhibition on the antitumour activity of immune cells in mice bearing melanomas has revealed potential targets for cancer therapy. See Article p.52 Immunotherapy is an important area of cancer research, and recent work has shown that targeting inhibitory receptors on T cells can result in clinical benefit in patients with advanced cancers. A major problem in the field is the difficulty of finding potential targets. Here Kai Wucherpfennig and colleagues show that in vivo discovery of therapeutic targets is a practical proposition by using short hairpin RNA (shRNA) screening to identify genes that modify the action of tumour-infiltrating CD8 T cells in tumour-bearing mice. They identify the regulatory phosphatase Ppp2r2d as a target and show that knockdown of Ppp2r2d in T cells enabled their accumulation in tumours and significantly delayed tumour growth.