Immune checkpoint inhibition in lymphoid disease

Abstract

It has long been understood that the immune system has intrinsic anti-tumour activity in humans, and that a key mechanism of tumour progression is the ability of a tumour to escape this immune surveillance. A number of attempts have been made to harness this anti-tumour immunity in both solid tumour oncology and haematological malignancies with variable success. Examples include the use of allogeneic stem cell transplantation and donor lymphocyte infusion in haematological cancer and vaccine studies in solid tumours. Enhanced signalling of the Programmed cell death-1 (PDCD1, PD-1)/cytotoxic T-lymphocyte-associated protein 4 (CTLA4) ‘immune checkpoint’ pathway has emerged recently as a critical mechanism by which tumours can escape the natural anti-tumour immune response. As such, novel therapies have been developed to help enhance this natural immunity by switching off the PDCD1/CTLA4 immune checkpoint pathway. The following review will discuss the pathobiology of these pathways and the exciting new data now available in lymphoid malignancies.