Decreased levels of circulating cytokines VEGF, TNF-β and IL-15 indicate PD-L1 overexpression in tumours of primary breast cancer patients

• Published in: Scientific reports Vol. 11; no. 1; p. 1294
• Main Authors: Cierna, Zuzana, Smolkova, Bozena, Cholujova, Dana, Gronesova, Paulina, Miklikova, Svetlana, Cihova, Marina, Plava, Jana, Mego, Michal
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14-01-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 692/4028/67/1347; 692/53/2422; Biomarkers; Breast cancer; Cytokines; Humanities and Social Sciences; Immunohistochemistry; Immunological tolerance; Interleukin 15; Microenvironments; multidisciplinary; Multivariate analysis; PD-L1 protein; Science; Science (multidisciplinary); Tumor necrosis factor; Tumors; Vascular endothelial growth factor
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-80351-9

Programmed death ligand 1 (PD-L1) overexpression has been associated with poor clinical outcomes in several human cancers whose increased malignant behaviour might be related to PD-L1 mediated systemic immunological tolerance. This study aims to verify if circulating cytokines may serve as a proxy for non-invasive identification of sensitive prognostic biomarkers reflecting tumour and its microenvironment. Immunohistochemistry was used to measure PD-L1 expression in tumour tissue sections of 148 chemonaïve breast cancer (BC) patients. The panel of 51 cytokines was analysed using multiplex bead arrays. High PD-L1 expression in tumours was associated with shorter progression-free survival (HR 3.25; 95% CI 1.39–7.61; P = 0.006) and low circulating levels of three multifunctional molecules; VEGF, TNF-β and IL-15 (P = 0.001). In multivariate analysis, patients with low VEGF had 4.6-fold increased risk of PD-L1 overexpression (P = 0.008), present in 76.5% of patients with all these three cytokines below the median (vs. 35.6% among the others; P = 0.002). The area under the curve value of 0.722 (95% CI 0.59–0.85; P = 0.004) shows that this combination of cytokines has a moderate ability to discriminate between PD-L1 high vs. PD-L1 low patients. Plasma cytokines, therefore, could serve as potential non-invasive biomarkers for the identification of high-risk BC cases.