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Int J Mol Sci ; 20(7)2019 Apr 02.
Article in English | MEDLINE | ID: mdl-30986912

ABSTRACT

PD-L1 tumor expression is a widely used biomarker for patient stratification in PD-L1/PD-1 blockade anticancer therapies, particularly for lung cancer. However, the reliability of this marker is still under debate. Moreover, PD-L1 is widely expressed by many immune cell types, and little is known on the relevance of systemic PD-L1⁺ cells for responses to immune checkpoint blockade. We present two clinical cases of patients with non-small cell lung cancer (NSCLC) and PD-L1-negative tumors treated with atezolizumab that showed either objective responses or progression. These patients showed major differences in the distribution of PD-L1 expression within systemic immune cells. Based on these results, an exploratory study was carried out with 32 cases of NSCLC patients undergoing PD-L1/PD-1 blockade therapies, to compare PD-L1 expression profiles and their relationships with clinical outcomes. Significant differences in the percentage of PD-L1⁺ CD11b⁺ myeloid cell populations were found between objective responders and non-responders. Patients with percentages of PD-L1⁺ CD11b⁺ cells above 30% before the start of immunotherapy showed response rates of 50%, and 70% when combined with memory CD4 T cell profiling. These findings indicate that quantification of systemic PD-L1⁺ myeloid cell subsets could provide a simple biomarker for patient stratification, even if biopsies are scored as PD-L1 null.


Subject(s)
B7-H1 Antigen/antagonists & inhibitors , Biomarkers, Tumor/metabolism , Immunotherapy , Lung Neoplasms/immunology , Lung Neoplasms/therapy , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , B7-H1 Antigen/metabolism , CD4-Positive T-Lymphocytes/metabolism , Female , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/drug therapy , Male , Middle Aged , Programmed Cell Death 1 Receptor/metabolism
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