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

被引:19
作者
Dart, Sarah J. [1 ,2 ]
Cook, Alistair M. [1 ,2 ,4 ]
Millward, Michael J. [1 ,3 ]
McDonnell, Alison M. [1 ,2 ]
Chin, Wee L. [1 ,2 ,3 ,4 ]
Hakeem, Muhammad U. [3 ]
Meniawy, Tarek M. [1 ,3 ]
Bowyer, Samantha E. [1 ,3 ]
机构
[1] Univ Western Australia, Fac Hlth & Med Sci, Perth, WA, Australia
[2] Natl Ctr Asbestos Related Dis, Perth, WA, Australia
[3] Sir Charles Gairdner Hosp, Dept Med Oncol, Perth, WA, Australia
[4] Inst Resp Hlth, Nedlands, WA 6009, Australia
关键词
PREDICTIVE BIOMARKERS; COMBINED NIVOLUMAB; IPILIMUMAB; PEMBROLIZUMAB; CHEMOTHERAPY; ANTI-CTLA-4; PD-1/PD-L1; DOCETAXEL; ANTIBODY; SAFETY;
D O I
10.1038/s41598-021-93479-z
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:11
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