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Immunotherapy

Checkpoint parley

Nature Reviews Cancer volume 15, page 3 (2015)Cite this article

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Immune checkpoint blockade has emerged as one of the most promising strategies for tackling solid tumours. Although there have been encouraging clinical results, such as in patients with metastatic melanoma, the factors that determine responsiveness to this type of therapy remain unclear. Five recent studies published in Nature and two studies from the New England Journal of Medicine now advance our understanding of therapies that target the programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte antigen 4 (CTLA4) immune checkpoints.

The studies also identified biomarkers that can predict the success of immune checkpoint blockade. Tumeh et al. characterized samples that had been taken from patients with metastatic melanoma before and during therapy with the PD1-specific antibody pembrolizumab; they showed that patients who responded to pembrolizumab had higher pre-existing numbers of CD8+, PD1+ and PDL1+ cells in the tumour microenvironment. The reports by Powles et al., Herbst et al. and Robert et al. also found that high levels of PDL1 expression in the tumour microenvironment were predictive of a better clinical response to therapies targeting the PD1–PDL1 pathway. High levels of PDL1 expression by tumour-infiltrating immune cells were reported to be the best predictor of treatment efficacy, but increased expression of CTLA4 and greater levels of CD8+ T cell proliferation in the tumour were also associated with a better response to therapies targeting PD1 or PDL1.

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References

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  1. Senior Editor, Nature Reviews Immunology,

    Yvonne Bordon

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  1. Yvonne Bordon
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Bordon, Y. Checkpoint parley. Nat Rev Cancer 15, 3 (2015). https://doi.org/10.1038/nrc3880

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