PD-L1 Expression in Systemic Immune Cell Populations as a Potential Predictive Biomarker of Responses to PD-L1/PD-1 Blockade Therapy in Lung Cancer

• Main Authors: Ana Bocanegra, Gonzalo Fernandez-Hinojal, Miren Zuazo-Ibarra, Hugo Arasanz, Maria Jesus Garcia-Granda, Carlos Hernandez, Maria Ibañez, Berta Hernandez-Marin, Maite Martinez-Aguillo, Maria Jose Lecumberri, Angela Fernandez de Lascoiti, Lucia Teijeira, Idoia Morilla, Ruth Vera, David Escors, Grazyna Kochan
• Format: Article
• Language: English
• Published: MDPI AG 2019-04-01
• Series: International Journal of Molecular Sciences
• Subjects: PD-L1; biomarker; lung cancer; immunotherapy; immune checkpoint blockade
• Online Access: https://www.mdpi.com/1422-0067/20/7/1631

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.