Resistance to PD-1 Checkpoint Blockade

Michelle Krogsgaard, PhD, associate professor, Department of Pathology, NYU Langone's Perlmutter Cancer Center, discusses mechanisms of resistance to PD-1 checkpoint blockade.

Researchers are trying to understand why patients become resistant to checkpoint inhibitors. T cells are the focus, Krogsgaard says, since that is what checkpoint blockade targets. She says they are using a variety of biophysical and proteomic techniques to understand if there are alterations in the downstream signaling cascades in the T cells. This could lead to the identification of new targets.

Specifically, researchers isolate receptors from the cells and measure their interactions with other signaling proteins. They also take samples from patients who derived benefit from checkpoint blockade and from those who were resistant. They then isolate T cells from patients and determine whether there is a deficiency in the signaling pathways.