Resistance to Immunotherapy: Mechanisms and Means for Overcoming

Immune checkpoint blockade transformed cancer therapy during the last decade. However, durable responses remain uncommon, early and late relapses occur over the course of treatment, and many patients with PD-L1-expressing tumors do not respond to PD-(L)1 blockade. In addition, while some malignancies exhibit inherent resistance to treatment, others develop adaptations that allow them to evade antitumor immunity after a period of response. It is crucial to understand the pathophysiology of the tumor-immune system interplay and the mechanisms of immune escape in order to circumvent primary and acquired resistance. Here we provide an outline of the most well-defined mechanisms of resistance and shed light on ongoing efforts to reinvigorate immunoreactivity.