Pseudoprogression and Immune-Related Response in Solid Tumors

Abstract

Emerging cancer therapeutics target the immune system, stimulating host antitumor response. Tumor cells generate an immunosuppressive milieu with multiple mechanisms to evade immune destruction, including disruption of effective antigen presentation, reduction of effector T-cell function, and upregulation of pathways that promote tolerance and T-cell anergy.1 The programmed death (PD) -1/PD ligand-1 (PD-L1) pathway is a critical component of tumor-mediated immunosuppression. Antibodies to PD-1 and PD-L1 have shown potential clinical benefit in advanced solid tumors.2 The US Food and Drug Administration approved the PD-1 inhibitors pembrolizumab and nivolumab for metastatic melanoma and also recently approved nivolumab for the treatment of metastatic squamous non–small-cell lung cancer. The US Food and Drug Administration has also designated the PD-L1 inhibitor MPDL3280A as a breakthrough therapy for bladder cancer and non–small-cell lung cancer. These drugs and additional immune checkpoint inhibitors are currently under investigation in multiple clinical trials as single-agent therapy and also in combination with other agents.