التفاصيل البيبلوغرافية
| العنوان: |
PD-L1 on peripheral blood T lymphocytes is prognostic in patients with non-small cell lung cancer (NSCLC) treated with EGFR inhibitors. |
| المؤلفون: |
Meniawy, Tarek M.1,2,3 tarek.meniawy@uwa.edu.au, Lake, Richard A.1,3, McDonnell, Alison M.1,3, Millward, Michael J.1,2, Nowak, Anna K.1,2,3 |
| المصدر: |
Lung Cancer (01695002). Mar2016, Vol. 93, p9-16. 8p. |
| مصطلحات موضوعية: |
*NON-small-cell lung carcinoma, *EPIDERMAL growth factor receptors, *PROTEIN-tyrosine kinase inhibitors, *T cells, *IMMUNOTHERAPY, *FLOW cytometry, *HEALTH outcome assessment, *THERAPEUTICS |
| مستخلص: |
Objectives The immune effects of EGFR tyrosine kinase inhibitors (EGFR-TKIs) are poorly understood. Identifying immune biomarkers could guide patient selection and optimisation of EGFR-TKI-immunotherapy combinations. Materials and methods 33 patients with NSCLC treated with an EGFR-TKI were prospectively enrolled. Peripheral blood mononuclear cells were collected pre-treatment, and after 1, 3 and 8 weeks. Flow cytometry was used to identify immune cell subsets, including PD-1 and PD-L1 expressing T cells. Immune parameters were correlated with clinical outcomes. Results Compared to healthy donors ( n = 10), patients had higher pre-treatment proportions of proliferating and PD-L1 + CD3 + T cells ( p < 0.001). Compared to patients with an EGFR mutation ( n = 12), patients without a known mutation ( n = 21) had higher proportions of proliferating CD4 + and PD-L1 + CD3 + T cells ( p = 0.03). There was a significant increase in PD-L1 + T cells after 1 week of EGFR-TKI in patients whose disease progressed compared to non-progressors. Patients with higher PD-L1 + CD3 + T cells at 1-week were more likely to progress (OR 30.3, p < 0.01) and had shorter PFS (1.6 vs. 8.8 m; p < 0.01) and OS (3.8 vs 23.2 m; p < 0.001) than those with fewer PD-L1 + CD3 + T cells. On multivariate analysis, high PD-L1 + CD3 + T cells was the only independent predictor for PFS (HR 3.7, p = 0.01), while for OS independent predictors were high PD-L1 + CD3 + T cells (HR 6.5, p < 0.01) and EGFR-negative status (HR 3.3, p = 0.04). Conclusions There was a significant correlation between PD-L1 expression on peripheral T cells and clinical outcomes in EGFR-TKI-treated NSCLC. This warrants further validation as a blood-based biomarker that may identify candidates for PD-1 inhibitors or immunotherapy-EGFR-TKI combinations. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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