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Elements of cancer immunity and the cancer–immune set point

Abstract

Immunotherapy is proving to be an effective therapeutic approach in a variety of cancers. But despite the clinical success of antibodies against the immune regulators CTLA4 and PD-L1/PD-1, only a subset of people exhibit durable responses, suggesting that a broader view of cancer immunity is required. Immunity is influenced by a complex set of tumour, host and environmental factors that govern the strength and timing of the anticancer response. Clinical studies are beginning to define these factors as immune profiles that can predict responses to immunotherapy. In the context of the cancer-immunity cycle, such factors combine to represent the inherent immunological status — or 'cancer–immune set point' — of an individual.

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Figure 1: Cancer mutations, neoantigens and immunogenicity.
Figure 2: Compartmentalization of cancer–immune biomarkers.
Figure 3: Cancer-immune phenotypes.
Figure 4: Multivariate factors influence tolerance and immunity.
Figure 5: Factors that influence the cancer–immune set point.

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Acknowledgements

The authors would like to thank S. Turley, M. Albert, W. Grossman, L. Delamarre, P. Hegde, A. Murthy, J. Grogan, G. Jarmy, L. Molinero, D. Berger and K. McClellan for their review of and input into this manuscript, and L. Molinero for coining the terms immune desert and hyperexhausted. Medical writing assistance was provided by L. Yauch of Health Interactions and paid for by F. Hoffmann-La Roche.

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Correspondence to Ira Mellman.

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D.S.C. and I.M. are employees of Genentech, Inc.

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Reprints and permissions information is available at www.nature.com/reprints.

Reviewer Information Nature thanks G. Dranoff, W.-H. Fridman and J. Wolchok for their contribution to the peer review of this work.

Supplementary Information is linked to the online version of the paper at go.nature.com/2iiur42.

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Supplementary Figure 1

Cancer immunotherapy-based combination studies underway in 2016. (DOC 479 kb)

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Chen, D., Mellman, I. Elements of cancer immunity and the cancer–immune set point. Nature 541, 321–330 (2017). https://doi.org/10.1038/nature21349

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