Cited by 369Cancer Immunotherapy and BiomarkersImmunotherapy and Immune ResponsesT-cell and B-cell Immunology

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Targeting Programmed Cell Death -1 (PD-1) and Ligand (PD-L1): A new era in cancer active immunotherapy

Constantinidou, Anastasia, Alifieris, Constantinos, Trafalis, Dimitrios T.·2019·Pharmacology & Therapeutics

DOI 10.1016/j.pharmthera.2018.09.008

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Abstract

Improved understanding of the immune system and its role in cancer development and progression has led to impressive advances in the field of cancer immunotherapy over the last decade. Whilst the field is rapidly evolving and the list of drugs receiving regulatory approval for the treatment of various cancers is fast growing, the group of PD1- PDL-1 inhibitors is establishing a leading role amongst immunomodulatory agents. PD1- PDL-1 inhibitors act against pathways involved in adaptive immune suppression resulting in immune checkpoint blockade. Within the last four years two PD-1 and three PD-L1 inhibitors have been utilized in clinical practice against a variety of malignancies. Focus was initially placed on targeting cancers considered immunogenic such as melanoma, renal and lung cancers but subsequently the application expanded to include amongst others Hodgkin Lymphoma, urothelial as well as head and neck cancer. This article provides a comprehensive review of the early and late phase trials that led to the regulatory approval of all five PD1- PDL-1 inhibitors in the corresponding cancer types. It presents available data on the combinations of PD1- PDL-1 inhibitors with other therapies (immunotherapy, targeted therapy and chemotherapy), the toxicity profile of the PD1- PDL-1 inhibitors and ongoing trials testing the efficacy of these agents in cancer types beyond those that have been addressed already. Finally, current and future challenges in the application of PD-1 and PD-L1 inhibitors are discussed with emphasis on the role of predictive biomarkers.

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Authors: Constantinidou, A., Alifieris, C., & Trafalis, D. T.
Affiliations: University of Cyprus (CY)
National and Kapodistrian University of Athens (GR)
Corresponding author: Trafalis, Dimitrios T.
ORCID: Constantinidou, Anastasia
Alifieris, Constantinos
Trafalis, Dimitrios T.
Venue: Pharmacology & Therapeutics
Publisher: Elsevier BV
Published: 2019-02
Volume: 194
Pages: 84-106
ISSN: 0163-7258 (ISSN-L)
DOI: 10.1016/j.pharmthera.2018.09.008
OpenAlex: W2894101188
Cited by: 342
References: 230
Citations by year: 2026: 13 · 2025: 16 · 2024: 43 · 2023: 51 · 2022: 58 · 2021: 72 · 2020: 53 · 2019: 35
FWCI: 4.31
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Pharmacology & Therapeutics (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords: PD-1 inhibitors, PD-L1 inhibitors, immune checkpoint blockade, cancer immunotherapy, melanoma, renal cell carcinoma, lung cancer, Hodgkin's disease, urothelial carcinoma, head and neck cancer, combination therapy, toxicity profile, predictive biomarkers, regulatory approval
MeSH terms: Antineoplastic Agents, Immunological, Animals, Humans, Immunotherapy, Neoplasms, B7-H1 Antigen, Programmed Cell Death 1 Receptor

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Targeting Programmed Cell Death -1 (PD-1) and Ligand (PD-L1): A new era in cancer active immunotherapy

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