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A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization

Open access
Sanmamed, Miguel F., Chen, Lieping·2018·Cell

Abstract

Harnessing an antitumor immune response has been a fundamental strategy in cancer immunotherapy. For over a century, efforts have primarily focused on amplifying immune activation mechanisms that are employed by humans to eliminate invaders such as viruses and bacteria. This “immune enhancement” strategy often results in rare objective responses and frequent immune-related adverse events (irAEs). However, in the last decade, cancer immunotherapies targeting the B7-H1/PD-1 pathway (anti-PD therapy), have achieved higher objective response rates in patients with much fewer irAEs. This more beneficial tumor response-to-toxicity profile stems from distinct mechanisms of action that restore tumor-induced immune deficiency selectively in the tumor microenvironment, here termed “immune normalization,” which has led to its FDA approval in more than 10 cancer indications and facilitated its combination with different therapies. In this article, we wish to highlight the principles of immune normalization and learn from it, with the ultimate goal to guide better designs for future cancer immunotherapies.

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Metadata

Authors
Sanmamed, M. F., & Chen, L.
Venue
Cell
Publisher
Elsevier BV
Published
2018-10
Volume
175
Issue
2
Pages
313-326
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2894717949
Cited by
1,392
References
32
FWCI
47.27
Type
journal article
Language
en
Open access
bronze

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Sanmamed, M. F., & Chen, L. (2018). A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization. Cell. https://doi.org/10.1016/j.cell.2018.09.035

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