Micromanaging the microenvironment

A Massachusetts team has designed an in vivo shRNA screen to discover immunosuppressive tumor targets that can be blocked to improve the efficacy of T cell immunotherapies.¹ The screening system shows that current checkpoint inhibitors are barely scratching the surface of potential targets to modulate and may enable new directions in immunotherapy enhancement.

Targets for modulating immune responses, such as CTLA-4 (CD152) and programmed cell death 1 (PDCD1; PD-1; CD279), are typically identified in vitro and tested in animal models later in the discovery process. The Massachusetts team thought it would be useful to identify targets directly in animals to account for the complex interactions of immune cells within tissues...