The future of cancer therapy: selecting patients likely to respond to PD1/L1 blockade

Abstract

It is conceivable that, in the near future, an assay that defines the likelihood of a patient with advanced cancer to respond to immunotherapy based on PD1/L1 blockade will be the initial decision point to select the treatment of patients with any cancer type.

Figure 1

Potential interactions between cancer cells and T cells limited by PD-1/PD-L1. A) Adaptive immune resistance happens when a T cell with a T cell receptor (TCR) specific for a tumor antigen is activated upon antigen recognition on the surface of a cancer cell. Upon activation, the T cell expresses PD-1 and also releases interferons. The interferons are recognized by the cancer cell and lead to the adaptive surface expression of PD-L1. In this case there is a co-localization of T cells, tumor cells and PD-1 and PD-L1. B) In some instances, oncogenic events in the cancer cells lead to constitutive PD-L1 expression, which may be independent of the presence of tumor antigen-specific T cells. C) In other scenarios, T cells may infiltrate cancers in an environment that leads to their inactivation, not triggering the production of interferons and therefore not resulting in the adaptive expression of PD-L1.