Changes in expression of PD-L1 on peripheral T cells in patients with melanoma and lung cancer treated with PD-1 inhibitors

Sarah J Dart; Alistair M Cook; Michael J Millward; Alison M McDonnell; Wee L Chin; Muhammad U Hakeem; Tarek M Meniawy; Samantha E Bowyer

doi:10.1038/s41598-021-93479-z

Changes in expression of PD-L1 on peripheral T cells in patients with melanoma and lung cancer treated with PD-1 inhibitors

Sci Rep. 2021 Jul 28;11(1):15312. doi: 10.1038/s41598-021-93479-z.

Authors

Sarah J Dart^#^{1

2}, Alistair M Cook^{1

2

3}, Michael J Millward^{1

4}, Alison M McDonnell^{1

2}, Wee L Chin^{1

2

4

3}, Muhammad U Hakeem⁴, Tarek M Meniawy^#^{1

4}, Samantha E Bowyer^{5

6}

Affiliations

¹ Faculty of Health and Medical Sciences, The University of Western Australia, Perth, WA, Australia.
² National Centre for Asbestos Related Diseases, Perth, WA, Australia.
³ Institute for Respiratory Health, Nedlands, WA, 6009, Australia.
⁴ Department of Medical Oncology, Sir Charles Gairdner Hospital, Perth, WA, Australia.
⁵ Faculty of Health and Medical Sciences, The University of Western Australia, Perth, WA, Australia. [email protected].
⁶ Department of Medical Oncology, Sir Charles Gairdner Hospital, Perth, WA, Australia. [email protected].

^# Contributed equally.

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

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 / biosynthesis*
B7-H1 Antigen / genetics
Carcinoma, Non-Small-Cell Lung / drug therapy
Carcinoma, Non-Small-Cell Lung / metabolism*
Female
Gene Expression Regulation, Neoplastic / drug effects*
Humans
Immune Checkpoint Inhibitors / adverse effects
Immune Checkpoint Inhibitors / pharmacology*
Immune Checkpoint Inhibitors / therapeutic use
Ipilimumab / administration & dosage
Ipilimumab / adverse effects
Ipilimumab / pharmacology
Kaplan-Meier Estimate
Lung Neoplasms / drug therapy
Lung Neoplasms / metabolism*
Male
Melanoma / drug therapy
Melanoma / metabolism*
Molecular Targeted Therapy*
Neoplasm Proteins / antagonists & inhibitors
Neoplasm Proteins / biosynthesis*
Neoplasm Proteins / genetics
Nivolumab / administration & dosage
Nivolumab / adverse effects
Nivolumab / pharmacology
Nivolumab / therapeutic use
Pilot Projects
Progression-Free Survival
Prospective Studies
T-Lymphocytes / drug effects*
T-Lymphocytes, Regulatory / drug effects

Substances

Antibodies, Monoclonal, Humanized
B7-H1 Antigen
CD274 protein, human
Immune Checkpoint Inhibitors
Ipilimumab
Neoplasm Proteins
Nivolumab
pembrolizumab