Since 2014, programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) checkpoint inhibitors have been approved by various regulatory agencies for the treatment of multiple cancers including melanoma, lung cancer, urothelial carcinoma, renal cell carcinoma, head and neck cancer, classical Hodgkin lymphoma, colorectal cancer, gastroesophageal cancer, hepatocellular cancer, and other solid tumors.
Here, we report the complex structure of PD-1 with toripalimab, a mAb that is approved by China National Medical Products Administration as a second-line treatment for melanoma and is under multiple Phase 1-Phase 3 clinical trials in both China and the US.
The programmed cell death protein-1/programmed cell death ligand 1 expression, CD3+ T cell infiltration, NY-ESO-1 expression, and microsatellite instability phenotype in primary cutaneous melanoma and mucosal melanoma and their clinical significance and prognostic value: a study of 89 consecutive cases.
From January to April 2018, 978 perfusions of anti-programmed cell death protein 1 were administered at our institution including 560 perfusions of nivolumab in 103 patients and 418 perfusions of pembrolizumab in 125 patients mainly treated for lung cancer and melanoma.
Neutralizing antibodies targeting immune checkpoint programmed cell death protein 1 (PD-1) or its ligand (PD-L1) have been particularly successful for tumor types with limited therapeutic options such as melanoma and lung cancer.
Peripheral blood sPD-1 level and PD-1 positivity in patients with liver cancer and melanoma cancer were higher than those in patients with renal cell carcinoma and breast cancer.
In recent years, treatment of melanoma and a range of other deadly cancers has involved immunotherapy with programmed cell death protein-1 (PD-1)/PD-1 ligand (PD-L1) checkpoint blockade which has improved survival.
In addition, CDK4/6 inhibitor (palbociclib) treatment increased PD-L1 protein levels and enhanced efficacy (<i>P</i> < 0.05) in the C57BL/6-hPD-1melanoma cell and the HIS PDX model.
Nivolumab is widely used to treat several late-stage malignancies such as melanoma and non-small-cell lung cancer by inhibiting the interaction between the programmed cell death protein-1 and its ligand.
Finally we show, using either a genetic or pharmacological approach, that induction of UCP2 sensitizes melanomas to programmed cell death protein-1 blockade treatment and elicits effective anti-tumor responses.
In addition, the combination of antibodies to CTLA-4 (ipilimumab) and to PD-1 (nivolumab) has been found to confer a survival benefit in patients with melanoma or renal cell carcinoma.
The introduction of the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) immune checkpoint inhibitors and their subsequent listing on the Pharmaceutical Benefits Scheme for use in metastatic melanomas, renal cell carcinomas and non-small-cell lung cancers has resulted in routine use of these agents in oncology practices, including in regional areas.
Anti-PD-1 or anti-PD-L1 therapy has induced tumor regression and improved clinical outcome in patients with different tumor entities, including melanoma, non-small-cell lung cancer, and renal cell carcinoma.
Immune checkpoint inhibitors targeting the cytotoxic T lymphocyte-associated antigen-4 and programmed cell death-1 receptors have transformed the treatment of melanoma and other cancers.
Besides its prognostic significance, after approval of cytotoxic T lymphocyte antigen 4, programmed cell death-1 and programmed death-1 ligand antibodies for the treatment of melanoma, the assessment of immune infiltrate composition has become even more captivating, as it could provide new target molecules and new biomarkers for predicting the effect of the treatment and disease outcome in patients treated with immunotherapy.
AHR activation induces the expression of resistance genes against the inhibitors of V600E mutated B-Raf proto-oncogene, serine/threonine kinase (BRAF) in melanoma and upregulation of programmed cell death protein 1 (PD-1) in tumor-infiltrating T cells surrounding melanoma.
ICIs targeting the Programmed cell death protein 1 (PD-1) cell surface receptor or its ligand PD-L1 are particularly effective, with clinical studies reporting powerful and durable therapeutic impact against many cancer types, including melanoma and non-small cell lung cancer.
We evaluated LAG-3 and TIGIT protein expression patterns, correlated these patterns with programmed cell death 1 (PD-1) protein expression, and determined their effects on clinicopathologic characteristics and biologic responses in melanoma.
Specific PD-1 blockades were approved for treatment of melanoma in 2014 and for treatment of non-small-cell lung cancer in 2015 in the United States, European Union, and Japan.
The relative treatment efficacy was similar according to sex (male vs female, <i>P</i>=0.60), performance status (0 vs ≥1, <i>P</i>=0.68), tumor histology (squamous NSCLC vs non-squamous NSCLC vs melanoma vs urothelial carcinoma vs head and neck carcinoma vs renal cell carcinoma, <i>P</i>=0.64), and treatment type (PD-1 inhibitor vs PD-L1 inhibitor, <i>P</i>=0.36).
Additionally, expression of PD-L1 on dendritic cells and macrophages in ovarian cancer and melanoma patients correlated with the efficacy of treatment with either anti-PD-1 alone or in combination with anti-CTLA-4.