期刊
SCIENCE
卷 359, 期 6382, 页码 1350-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aar4060
关键词
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资金
- NIH [R35 CA197633, P01 CA168585, P30 CA016042, R01 CA056821, P30 CA008748]
- Ressler Family Fund
- Grimaldi Family Fund
- Garcia-Corsini Family Fund
- Swim Across America
- Ludwig Cancer Research
- Hazen-Polsky Family Fund
- Hogan Family Fund
- Live4Life Foundation
- Etta Weinheim Fund
The release of negative regulators of immune activation (immune checkpoints) that limit antitumor responses has resulted in unprecedented rates of long-lasting tumorresponses 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-g signaling pathways. New-generation combinatorial therapies may overcome resistance mechanisms to immune checkpoint therapy.
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