Immune checkpoint inhibitors: recent progress and potential biomarkers

• Published in: Experimental & molecular medicine Vol. 50; no. 12; pp. 1 - 11
• Main Authors: Darvin, Pramod, Toor, Salman M., Sasidharan Nair, Varun, Elkord, Eyad
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2018; Springer Nature B.V; Nature Publishing Group; 생화학분자생물학회
• Subjects: 631/250/251; 692/53/2423; Animals; Antibodies, Monoclonal - therapeutic use; B7-H1 Antigen - immunology; Biomarkers; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer immunotherapy; Cancer therapies; Clinical trials; CTLA-4 Antigen - immunology; CTLA-4 protein; Decision making; Epigenesis, Genetic; Humans; Immune checkpoint; Immune checkpoint inhibitors; Immune Tolerance; Immunity; Immunization; Immunotherapy - trends; Medical Biochemistry; Molecular Medicine; Monoclonal antibodies; Neoplasms - immunology; Neoplasms - therapy; Patients; PD-1 protein; PD-L1 protein; Programmed Cell Death 1 Receptor - immunology; Review; Review Article; Stem Cells; Treatment Outcome; Tumor Microenvironment; 생화학
• ISSN: 1226-3613; 2092-6413; 2092-6413
• DOI: 10.1038/s12276-018-0191-1

Cancer growth and progression are associated with immune suppression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. Monoclonal antibodies that target immune checkpoints provided an immense breakthrough in cancer therapeutics. Among the immune checkpoint inhibitors, PD-1/PD-L1 and CTLA-4 inhibitors showed promising therapeutic outcomes, and some have been approved for certain cancer treatments, while others are under clinical trials. Recent reports have shown that patients with various malignancies benefit from immune checkpoint inhibitor treatment. However, mainstream initiation of immune checkpoint therapy to treat cancers is obstructed by the low response rate and immune-related adverse events in some cancer patients. This has given rise to the need for developing sets of biomarkers that predict the response to immune checkpoint blockade and immune-related adverse events. In this review, we discuss different predictive biomarkers for anti-PD-1/PD-L1 and anti-CTLA-4 inhibitors, including immune cells, PD-L1 overexpression, neoantigens, and genetic and epigenetic signatures. Potential approaches for further developing highly reliable predictive biomarkers should facilitate patient selection for and decision-making related to immune checkpoint inhibitor-based therapies. Cancer immunotherapy: Markers of success Biomarkers that predict a patient’s response to cancer immunotherapy are being developed, and may allow individual tailoring of therapies. Cancer cells can suppress the immune system by activating immune checkpoints, signals that stop the immune system from attacking the host. Immunotherapy, a recently developed treatment, inactivates immune checkpoints, restoring the patient’s immune response against the tumor. Although promising, immunotherapy has a low response rate, and sometimes triggers severe auto-immune reactions. Eyad Elkord at Qatar Biomedical Research Institute in Qatar and coworkers have reviewed biomarkers that could be used to predict individual effects of immunotherapy, identifying nonresponders and preventing adverse immune reactions. They discuss markers based on factors such as immune response level and individual tumor genetics, among others. With further research and testing, these biomarkers could improve the efficacy of this promising new cancer therapy.