Comparative Analysis of Predictive Biomarkers for PD-1/PD-L1 Inhibitors in Cancers: Developments and Challenges

• Published in: Cancers 2021-12, Vol.14 (1), p.109
• Main Authors: Yang, Fang, Wang, Jacqueline F, Wang, Yucai, Liu, Baorui, Molina, Julian R
• Format: Article
• Language: English
• Subjects: Adverse events; Antibodies; Apoptosis; Biomarkers; Cancer therapies; Cell death; Chemotherapy; Clinical trials; Colorectal cancer; Comparative analysis; FDA approval; Immune checkpoint inhibitors; Immunotherapy; Lymphocytes; Melanoma; Metastasis; Mutation; Non-small cell lung carcinoma; Patients; PD-1 protein; PD-L1 protein; Response rates; Review; Small cell lung carcinoma; Tumor microenvironment; Tumors
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14010109

Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) have dramatically changed the landscape of cancer therapy. Both remarkable and durable responses have been observed in patients with melanoma, non-small-cell lung cancer (NSCLC), and other malignancies. However, the PD-1/PD-L1 blockade has demonstrated meaningful clinical responses and benefits in only a subset of patients. In addition, several severe and life-threatening adverse events were observed in these patients. Therefore, the identification of predictive biomarkers is urgently needed to select patients who are more likely to benefit from ICI therapy. PD-L1 expression level is the most commonly used biomarker in clinical practice for PD-1/PD-L1 inhibitors. However, negative PD-L1 expression cannot reliably exclude a response to a PD-1/PD-L1 blockade. Other factors, such as tumor microenvironment and other tumor genomic signatures, appear to impact the response to ICIs. In this review, we examine emerging data for novel biomarkers that may have a predictive value for optimizing the benefit from anti-PD-1/PD-L1 immunotherapy.