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

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 t...

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Main Authors: Sarah J. Dart, Alistair M. Cook, Michael J. Millward, Alison M. McDonnell, Wee L. Chin, Muhammad U. Hakeem, Tarek M. Meniawy, Samantha E. Bowyer
Format: Article
Language:English
Published: Nature Publishing Group 2021-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-93479-z
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spelling doaj-9d283bf0f1db4f83be33e5ef052e4ddd2021-08-01T11:23:13ZengNature Publishing GroupScientific Reports2045-23222021-07-0111111110.1038/s41598-021-93479-zChanges in expression of PD-L1 on peripheral T cells in patients with melanoma and lung cancer treated with PD-1 inhibitorsSarah J. Dart0Alistair M. Cook1Michael J. Millward2Alison M. McDonnell3Wee L. Chin4Muhammad U. Hakeem5Tarek M. Meniawy6Samantha E. Bowyer7Faculty of Health and Medical Sciences, The University of Western AustraliaFaculty of Health and Medical Sciences, The University of Western AustraliaFaculty of Health and Medical Sciences, The University of Western AustraliaFaculty of Health and Medical Sciences, The University of Western AustraliaFaculty of Health and Medical Sciences, The University of Western AustraliaDepartment of Medical Oncology, Sir Charles Gairdner HospitalFaculty of Health and Medical Sciences, The University of Western AustraliaFaculty of Health and Medical Sciences, The University of Western AustraliaAbstract 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.https://doi.org/10.1038/s41598-021-93479-z
collection DOAJ
language English
format Article
sources DOAJ
author Sarah J. Dart
Alistair M. Cook
Michael J. Millward
Alison M. McDonnell
Wee L. Chin
Muhammad U. Hakeem
Tarek M. Meniawy
Samantha E. Bowyer
spellingShingle Sarah J. Dart
Alistair M. Cook
Michael J. Millward
Alison M. McDonnell
Wee L. Chin
Muhammad U. Hakeem
Tarek M. Meniawy
Samantha E. Bowyer
Changes in expression of PD-L1 on peripheral T cells in patients with melanoma and lung cancer treated with PD-1 inhibitors
Scientific Reports
author_facet Sarah J. Dart
Alistair M. Cook
Michael J. Millward
Alison M. McDonnell
Wee L. Chin
Muhammad U. Hakeem
Tarek M. Meniawy
Samantha E. Bowyer
author_sort Sarah J. Dart
title Changes in expression of PD-L1 on peripheral T cells in patients with melanoma and lung cancer treated with PD-1 inhibitors
title_short Changes in expression of PD-L1 on peripheral T cells in patients with melanoma and lung cancer treated with PD-1 inhibitors
title_full Changes in expression of PD-L1 on peripheral T cells in patients with melanoma and lung cancer treated with PD-1 inhibitors
title_fullStr Changes in expression of PD-L1 on peripheral T cells in patients with melanoma and lung cancer treated with PD-1 inhibitors
title_full_unstemmed Changes in expression of PD-L1 on peripheral T cells in patients with melanoma and lung cancer treated with PD-1 inhibitors
title_sort changes in expression of pd-l1 on peripheral t cells in patients with melanoma and lung cancer treated with pd-1 inhibitors
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2021-07-01
description 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.
url https://doi.org/10.1038/s41598-021-93479-z
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