Anti-programmed death receptor 1 immunotherapy in melanoma: rationale, evidence and clinical potential
Open Access
- 23 September 2014
- journal article
- review article
- Published by SAGE Publications in Therapeutic Advances in Medical Oncology
- Vol. 7 (1), 12-21
- https://doi.org/10.1177/1758834014551747
Abstract
Malignant melanoma is a significant public health problem; according to 2013 Surveillance, Epidemiology, and End Results data, its average incidence rate rose 2.6% each year for the last decade, and it is now the fifth most common cancer diagnosis in the United States. The rising incidence and historical poor response to chemotherapy have led to intense investigation of novel treatments for melanoma, including therapies to improve the immune-mediated destruction of cancer cells. Among the hallmarks of malignancy is the ability to evade this process: while early stages of tumor growth can induce functional CD8+ T-cell responses, cancer cells become increasingly embedded in an immune-suppressive tumor stroma. In the tumor microenvironment, T-cell proliferation and effector function are impaired due to engagement of T-cell programmed death receptor 1 (PD-1) with programmed death receptor ligand (PD-L1) expressed by cancer cells and antigen-presenting cells, which blocks T-cell-mediated cytotoxicity. This receptor-ligand engagement thereby inhibits immunity, allows the tumor to continue to grow, and contributes to the phenomenon of ‘T-cell exhaustion’. One immunotherapy strategy currently under investigation is inhibition of the interaction between PD-L1 and PD-1, thereby overcoming a critical immune checkpoint to facilitate destruction of cancer cells. In this review we discuss the preclinical rationale for PD-1 pathway inhibition in cancer, recent results of clinical trials targeting PD-1 and PD-L1, and evaluate its potential as a future anticancer therapy.Keywords
This publication has 70 references indexed in Scilit:
- Transcriptional regulator early growth response gene 2 (Egr2) is required for T cell anergy in vitro and in vivoThe Journal of Experimental Medicine, 2012
- Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced CancerNew England Journal of Medicine, 2012
- Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in CancerNew England Journal of Medicine, 2012
- Colocalization of Inflammatory Response with B7-H1 Expression in Human Melanocytic Lesions Supports an Adaptive Resistance Mechanism of Immune EscapeScience Translational Medicine, 2012
- Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunityCurrent Opinion in Immunology, 2012
- The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti–PD-1 antibodyBlood, 2010
- Inhibition of Mutated, Activated BRAF in Metastatic MelanomaNew England Journal of Medicine, 2010
- Improved Survival with Ipilimumab in Patients with Metastatic MelanomaNew England Journal of Medicine, 2010
- Myeloid-derived suppressor cells as regulators of the immune systemNature Reviews Immunology, 2009
- Costimulatory molecule B7‐H1 in primary and metastatic clear cell renal cell carcinomaCancer, 2005