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Science. 2018 Mar 23;359(6382):1350-1355. doi: 10.1126/science.aar4060. Epub 2018 Mar 22.

Cancer immunotherapy using checkpoint blockade.

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Department of Medicine, Division of Hematology-Oncology; Department of Surgery, Division of Surgical Oncology; and Department of Molecular and Medical Pharmacology, Jonsson Comprehensive Cancer Center and Parker Institute for Cancer Immunotherapy, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Department of Medicine, Ludwig Center and Parker Institute for Cancer Immunotherapy at Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Weill Cornell Medical and Graduate Colleges, New York, NY 10065, USA.


The release of negative regulators of immune activation (immune checkpoints) that limit antitumor responses has resulted in unprecedented rates of long-lasting tumor responses in patients with a variety of cancers. This can be achieved by antibodies blocking the cytotoxic T lymphocyte-associated protein 4 (CTLA-4) or the programmed cell death 1 (PD-1) pathway, either alone or in combination. The main premise for inducing an immune response is the preexistence of antitumor T cells that were limited by specific immune checkpoints. Most patients who have tumor responses maintain long-lasting disease control, yet one-third of patients relapse. Mechanisms of acquired resistance are currently poorly understood, but evidence points to alterations that converge on the antigen presentation and interferon-γ signaling pathways. New-generation combinatorial therapies may overcome resistance mechanisms to immune checkpoint therapy.

[Indexed for MEDLINE]

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