1. Changes in expression of PD-L1 on peripheral T cells in patients with melanoma and lung cancer treated with PD-1 inhibitors.
- Author
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Dart SJ, Cook AM, Millward MJ, McDonnell AM, Chin WL, Hakeem MU, Meniawy TM, and Bowyer SE
- Subjects
- Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized adverse effects, Antibodies, Monoclonal, Humanized pharmacology, Antibodies, Monoclonal, Humanized therapeutic use, B7-H1 Antigen antagonists & inhibitors, B7-H1 Antigen genetics, Carcinoma, Non-Small-Cell Lung drug therapy, Female, Humans, Immune Checkpoint Inhibitors adverse effects, Immune Checkpoint Inhibitors therapeutic use, Ipilimumab administration & dosage, Ipilimumab adverse effects, Ipilimumab pharmacology, Kaplan-Meier Estimate, Lung Neoplasms drug therapy, Male, Melanoma drug therapy, Neoplasm Proteins antagonists & inhibitors, Neoplasm Proteins genetics, Nivolumab administration & dosage, Nivolumab adverse effects, Nivolumab pharmacology, Nivolumab therapeutic use, Pilot Projects, Progression-Free Survival, Prospective Studies, T-Lymphocytes, Regulatory drug effects, B7-H1 Antigen biosynthesis, Carcinoma, Non-Small-Cell Lung metabolism, Gene Expression Regulation, Neoplastic drug effects, Immune Checkpoint Inhibitors pharmacology, Lung Neoplasms metabolism, Melanoma metabolism, Molecular Targeted Therapy, Neoplasm Proteins biosynthesis, T-Lymphocytes drug effects
- Abstract
Advances in cancer immunology have increased the use of immune checkpoint inhibitors in clinical practice, however not all patients respond, and treatment can have severe side-effects. Blood-based immunological biomarkers are an attractive method for predicting which patients will respond to therapy, however, reliable biomarkers for immune checkpoint blockade are lacking. This study aimed to identify patients before or early in treatment who would best respond to PD-1 inhibitors. We hypothesised that higher baseline PD-L1 and/or PD-1 on peripheral blood T cells could predict radiological response to PD-1 inhibitors. This pilot prospective cohort study assessed 26 patients with melanoma or non-small cell lung cancer, treated with pembrolizumab, nivolumab, or nivolumab/ipilimumab combined. Response was assessed by RECIST 1.1. Peripheral blood lymphocytes collected at baseline, after one cycle, 10 weeks and at discontinuation of therapy were analysed by flow cytometry. Patients with a higher proportion of PD-L1
+ T cells at baseline had improved objective response to PD-1 inhibitor therapy, and patients with a lower proportion of regulatory T cells at baseline experienced more immune-related adverse events. These findings may prove useful to assist in clinical decision making. Further studies with larger cohorts are required to validate these findings., (© 2021. The Author(s).)- Published
- 2021
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