A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization.
By M. Sanmamed, Lieping Chen. Cell, 2018
1,171 citations recorded by the source corpus.
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.
Subfields: Immunology, Oncology
View Paper: https://www.semanticscholar.org/paper/7762bc6a673fea136556d51584e6dab76fa847a3
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Citations in the corpus
- Mechanisms controlling PD-L1 expression in cancer (2019, background): “Elucidating the roles of oncogenic pathways driving PD-L1 expression not only identifies the functional mechanisms but also offers a rationale for future combination therapy consisting immune checkpoint blockade antibodies and inhibitors targeting those oncogenic signaling pathways (Sanmamed and Che”