PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome
Top Cited Papers
Open Access
- 23 August 2017
- journal article
- review article
- Published by Frontiers Media SA in Frontiers in Pharmacology
- Vol. 8, 561
- https://doi.org/10.3389/fphar.2017.00561
Abstract
Several cancers are highly refractory to conventional chemotherapy. The survival of tumors in several cases is assisted by checkpoint immunomodulation to maintain the imbalance between immune surveillance and cancer cell proliferation. Check point antibody inhibitors, such as anti-PD-1/PD-L1, are a novel class of inhibitors that function as a tumor suppressing factor via modulation of immune cell-tumor cell interaction. These checkpoint blockers are rapidly becoming a highly promising cancer therapeutic approach that yields remarkable antitumor responses with limited side effects. In recent times, more than four check point antibody inhibitors have been commercialized for targeting PD-1, PDL-1, and CTLA-4. Despite the huge success and efficacy of the anti-PD therapy response, it is limited to specific types of cancers, which attributes to the insufficient and heterogeneous expression of PD-1 in the tumor microenvironment. Herein, we review the current landscape of the PD-1/PD-L1 mechanistic role in tumor immune evasion and therapeutic outcome for cancer treatment. We also review the current progress in clinical trials, combination of drug therapy with immunotherapy, safety, and future of check point inhibitors for multiple types of cancer.Keywords
Funding Information
- National Cancer Institute (1R21CA179652)
This publication has 67 references indexed in Scilit:
- PD-1 is a novel regulator of human B-cell activationInternational Immunology, 2012
- Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunityCurrent Opinion in Immunology, 2012
- Ipilimumab: An Anti-CTLA-4 Antibody for Metastatic MelanomaClinical Cancer Research, 2011
- IpilimumabNature Reviews Drug Discovery, 2011
- Hallmarks of Cancer: The Next GenerationCell, 2011
- Improved Survival with Ipilimumab in Patients with Metastatic MelanomaThe New England Journal of Medicine, 2010
- The PD‐1 pathway in tolerance and autoimmunityImmunological Reviews, 2010
- Programmed Death-1 Ligand 1 Interacts Specifically with the B7-1 Costimulatory Molecule to Inhibit T Cell ResponsesImmunity, 2007
- Immune Activation by Bacterial DNA: A New Genetic CodeImmunity, 1996
- Enhancement of Antitumor Immunity by CTLA-4 BlockadeScience, 1996