CTLA-4 and PD-1 Pathways
By E. Buchbinder, Anupam M. Desai. American Journal of Clinical Oncology, 2016
2,096 citations recorded by the source corpus.
The cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) immune checkpoints are negative regulators of T-cell immune function. Inhibition of these targets, resulting in increased activation of the immune system, has led to new immunotherapies for melanoma, non–small cell lung cancer, and other cancers. Ipilimumab, an inhibitor of CTLA-4, is approved for the treatment of advanced or unresectable melanoma. Nivolumab and pembrolizumab, both PD-1 inhibitors, are approved to treat patients with advanced or metastatic melanoma and patients with metastatic, refractory non-small cell lung cancer. In addition the combination of ipilimumab and nivolumab has been approved in patients with BRAF WT metastatic or unresectable melanoma. The roles of CTLA-4 and PD-1 in inhibiting immune responses, including antitumor responses, are largely distinct. CTLA-4 is thought to regulate T-cell proliferation early in an immune response, primarily in lymph nodes, whereas PD-1 suppresses T cells later in an immune response, primarily in peripheral tissues. The clinical profiles of immuno-oncology agents inhibiting these 2 checkpoints may vary based on their mechanistic differences. This article provides an overview of the CTLA-4 and PD-1 pathways and implications of their inhibition in cancer therapy.
Subfields: Immunology, Oncology
View Paper: https://www.semanticscholar.org/paper/c9c3c3d663a529752c4069c96a394e11c1f1250d
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
Citations in the corpus
- Cholesterol induces CD8+ T-cell exhaustion in the tumor microenvironment (2019, neutral): “, the combination of anti-PD-1 with anti-CTLA-4 (Buchbinder and Desai, 2016; Duraiswamy et al., 2013; Dyck and Mills, 2017), anti-PD-1 with anti-TIM-3 (Sakuishi et al.”
- DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy (2021, background): “Their receptors may interact with B7 to ensure the inactivation of T cells.(401) As a result, immune checkpoint blockade would promote adaptive immunity and inhibit cancer proliferation and growth.”