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Article

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

by
Ana Bocanegra
1,†,
Gonzalo Fernandez-Hinojal
2,†,
Miren Zuazo-Ibarra
1,†,
Hugo Arasanz
1,†,
Maria Jesus Garcia-Granda
1,
Carlos Hernandez
1,
Maria Ibañez
1,
Berta Hernandez-Marin
2,
Maite Martinez-Aguillo
2,
Maria Jose Lecumberri
2,
Angela Fernandez de Lascoiti
2,
Lucia Teijeira
2,
Idoia Morilla
2,
Ruth Vera
2,*,
David Escors
1,3,* and
Grazyna Kochan
1,*
1
Navarrabiomed-Fundacion Miguel Servet, IdISNA, Irunlarrea 3, 31008 Pamplona, Navarra, Spain
2
Department of Oncology, Complejo Hospitalario de Navarra, IdISNA, Irunlarrea 3, 31008 Pamplona, Navarra, Spain
3
Division of Infection and Immunity, University College London, 5 University Street, London WC1R 6JJ, UK
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally.
Int. J. Mol. Sci. 2019, 20(7), 1631; https://doi.org/10.3390/ijms20071631
Submission received: 6 March 2019 / Revised: 27 March 2019 / Accepted: 28 March 2019 / Published: 2 April 2019
(This article belongs to the Special Issue PD-L1, A Master Regulator of Immunity)
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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.
Keywords: PD-L1; biomarker; lung cancer; immunotherapy; immune checkpoint blockade PD-L1; biomarker; lung cancer; immunotherapy; immune checkpoint blockade
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MDPI and ACS Style

Bocanegra, A.; Fernandez-Hinojal, G.; Zuazo-Ibarra, M.; Arasanz, H.; Garcia-Granda, M.J.; Hernandez, C.; Ibañez, M.; Hernandez-Marin, B.; Martinez-Aguillo, M.; Lecumberri, M.J.; et al. 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. Int. J. Mol. Sci. 2019, 20, 1631. https://doi.org/10.3390/ijms20071631

AMA Style

Bocanegra A, Fernandez-Hinojal G, Zuazo-Ibarra M, Arasanz H, Garcia-Granda MJ, Hernandez C, Ibañez M, Hernandez-Marin B, Martinez-Aguillo M, Lecumberri MJ, et al. 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. International Journal of Molecular Sciences. 2019; 20(7):1631. https://doi.org/10.3390/ijms20071631

Chicago/Turabian Style

Bocanegra, Ana, 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, and et al. 2019. "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" International Journal of Molecular Sciences 20, no. 7: 1631. https://doi.org/10.3390/ijms20071631

APA Style

Bocanegra, A., Fernandez-Hinojal, G., Zuazo-Ibarra, M., Arasanz, H., Garcia-Granda, M. J., Hernandez, C., Ibañez, M., Hernandez-Marin, B., Martinez-Aguillo, M., Lecumberri, M. J., Fernandez de Lascoiti, A., Teijeira, L., Morilla, I., Vera, R., Escors, D., & Kochan, G. (2019). 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. International Journal of Molecular Sciences, 20(7), 1631. https://doi.org/10.3390/ijms20071631

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