Current clinical knowledge surrounding one of the most promising immune checkpoint pathways, namely programmed cell death-1 (PD-1) and its ligands PD-L1 and PD-L2, is reviewed in the context of head and neck squamous cell carcinoma. The results of two phase III clinical trials (KEYNOTE 040 and CheckMate 141) are critically examined. The utility of predictive biomarkers of response to immune checkpoint blockade, such as PD-L1/PD-L2 protein expression, interferon-gamma gene expression signatures, and mutational and neoantigen load, is discussed. Finally, we project future directions in the immuno-oncology field by discussing other promising predictive biomarkers as well as areas where the next advances are likely to take place, such as in the implementation of immune checkpoint inhibitors earlier in the course of cancer treatment and/or in combination therapies.
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Cover Image
Cover Image
Mapping gene signatures according to their expression in different immune landscapes of breast (BRCA), lung (LUAD) and colon (COAD) carcinoma, and melanoma (SKCM); signatures selectively expressed in the immune-active (ICR4) landscape are shown in red, those selectively expressed in the immune-silent (ICR1) landscape are shown as blue and those that are ubiquitously expressed independent of immune landscape are white. The image is based on Figure 1 in this issue's opening article (Lu et al., pages 411–419) in which the authors look at how cancer cells go through a conserved evolutionary bottleneck facing a Two-Option Choice to evade recognition by the immune competent host: they can either adopt a clean oncogenic process devoid of immunogenic stimuli (immune-silent tumors) or display an entropic biology prone to immune recognition (immune-active tumors).
Checkpoint cluster: biomarkers of response Available to Purchase
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