Cancer immunotherapy using checkpoint blockade

A Ribas, JD Wolchok - Science, 2018 - science.org
A Ribas, JD Wolchok
Science, 2018science.org
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 …
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.
AAAS