DISCOVERIES REPORTS (ISSN 2393249X), 2023, volume 6
ORIGINAL ARTICLE
CITATION: Immune checkpoint inhibitors and predictive biomarkers in checkpoint inhibition therapy. Discoveries Reports 2023; 6: e39. DOI: 10.15190/drep.2023.3
Immune checkpoint inhibitors and predictive biomarkers in checkpoint inhibition therapy
Sebastian-Timotei Nicolae 1,2 *
1 Southern Denmark University, Institute of Molecular Medicine, Odense, Denmark
2 Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
* Corresponding authors:
Sebastian-Timotei Nicolae, Carol Davila University of Medicine and Pharmacy, Bucharest Romania: Email: timoteisebastian.nicolae@gmail.co
Abstract
Cancer is one of the leading causes of death at a global scale. Many malignancies prove very hard to manage and current treatment methods, although effective to some extent, need improvement. Recently, Immune Checkpoints such as Programmed death receptor 1 (PD-1) and cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) have been a subject of great interest in cancer treatment. Blocking these receptors and their ligands enables the T-cells to recognize and destroy cancer cells easier, although this may not always be the case. Many studies have shown benefits of using immune checkpoint inhibitors (ICIs) over conventional chemotherapy, although there are some treatment-related adverse effects that are also to be taken into calculation. Most adverse reactions are autoimmune, given the fact that ICIs make the T-cells more reactive and block their co-inhibitory signals when activated. As with every treatment, predictive biomarkers for survival rate and response rate are very important, as such there has been a lot of research in order to find reliable markers that would allow an accurate estimate for the RR and OS of the patient. The most commonly used as of now are Tumor Mutation Burden, a marker that represents how many mutations cancer cells have suffered, as more of them would make the chances of immunogenic neoantigens being produced higher, Mismatch Repair Deficiency/ Microsatellite Instability, which is a marker that shows a tumor phenotype characterized by the production of immunogenic neoantigen, PD-L1 expression, which is a biomarker that has been linked with better response to ICI therapy, and Neutrophil to Lymphocyte Ratio, a value that expresses the balance between cancer induced inflammation and anti-tumor response of the body. In this review, I present FDA-approved checkpoint inhibitors and their applications, benefits and limitations of immune checkpoint blockade and predictive biomarkers and their accuracy and reliability. This manuscript offers insight into the uses and safety of checkpoint inhibitors as a cancer therapy, as well as the advantages and drawbacks of their most used biomarkers, thus allowing for a conclusive view on the topic. As such, Immune Checkpoint Inhibitors show great potential for cancer treatment. Predictive biomarkers for this new medicine are also promising and have proven reliable across many malignancies, although their ability to predict the response to ICI therapy can come under question in a number of scenarios.
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