Abstract
Cancer immunotherapies that target the T-cell immune checkpoints, such as CTLA-4, PD-1, and PD-L1, have shown unprecedented success for the treatment of a variety of malignancies. Although a significant number of patients benefit from immune checkpoint inhibitors (ICIs), only a subset of patients receives durable clinical benefit and many patients eventually develop therapeutic resistance after an initial response to ICIs. Additionally, these therapeutic agents often elicit immune-related adverse events that may result in substantial morbidities, some of which are life-threatening. Although the targets of ICIs are well defined, gaps in understanding the exact mechanism of action are a major impediment in efforts to improve ICI therapy. In this chapter, we summarize rationale for combining ICIs with other treatment and novel therapeutics modulating costimulatory and coinhibitory molecules on immune cells.
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