Cancer immunotherapy using checkpoint blockade
Top Cited Papers
- 23 March 2018
- journal article
- review article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 359 (6382), 1350-1355
- https://doi.org/10.1126/science.aar4060
Abstract
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.Funding Information
- National Cancer Institute (R35 CA197633)
- National Cancer Institute (P30 CA008748)
- National Cancer Institute (P30 CA016042)
- Parker Institute for Cancer Immunotherapy (N/A)
- Parker Institute for Cancer Immunotherapy (N/A)
- Ludwig Cancer Research (N/A)
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