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

• Published in: International journal of molecular sciences 2019-04, Vol.20 (7), p.1631
• Main Authors: Bocanegra, Ana, Fernandez-Hinojal, Gonzalo, Zuazo-Ibarra, Miren, Arasanz, Hugo, Garcia-Granda, Maria Jesus, Hernandez, Carlos, Ibañez, Maria, Hernandez-Marin, Berta, Martinez-Aguillo, Maite, Lecumberri, Maria Jose, Fernandez de Lascoiti, Angela, Teijeira, Lucia, Morilla, Idoia, Vera, Ruth, Escors, David, Kochan, Grazyna
• Format: Article
• Language: English
• Subjects: Antigen presentation; Biomarkers; Bladder cancer; Cancer therapies; CD11b antigen; Cell activation; Chemotherapy; Clinical outcomes; Cytotoxicity; Dendritic cells; Dyspnea; Flow cytometry; Gastric cancer; Head & neck cancer; Immune system; Immunotherapy; Kidney cancer; Lung cancer; Lymphocytes; Lymphocytes T; Medical prognosis; Melanoma; Metastasis; Microsatellite instability; Mutation; Non-small cell lung carcinoma; Patients; PD-1 protein; PD-L1 protein; Renal cell carcinoma; Squamous cell carcinoma; Suppressor cells; Tumors; Urothelial cancer; Urothelial carcinoma
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20071631

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.