Cancer immunotherapy: The dark side of PD-1 receptor inhibition

Abstract

Inhibiting the protein PD-1 can activate T cells that trigger immune responses against tumour cells. But it emerges that, in mice, this immunotherapy exacerbates a cancer that involves the T cells themselves.

Figure 1|. Dual roles for the PD-1 receptor protein.

a, PD-1 is expressed on the surface of immune cells called T cells. When PD-1 is bound by a ligand produced by tumour cells, PD-1 signalling renders the T cell inactive, preventing immune responses that would destroy the tumour. Treatment with an antibody to PD-1 blocks ligand binding and so PD-1 signalling, instead promoting the PI3K signalling pathway, which is involved in T-cell activation. As such, anti-PD-1 treatment triggers an immune response, b, Wartewig et al. have demonstrated that PD-1 signalling in a mouse model of T cell non-Hodgkin’s lymphoma prevents proliferation of cancerous T cells (the source of the PD-1 ligand was not defined). In these mice, anti-PD-1 treatment can aggravate disease by reactivating the cancerous cells to enable their continuous proliferation.