PRODUCTION OF MEMBRANE AND SOLUBLE PD-L1 BY LUNG TUMOR CELLS

Programmed Death-Ligand 1 (PD-L1) was first described as a membrane molecule expressed by antigen presenting cells to regulate T lymphocyte immune response through the engagement of its receptor PD-1 [1]. The observation that many tumors express PD-L1 to escape the immune surveillance augmented the interest in the immune checkpoint PD1:PD-L1 for its potential as tumor biomarker and molecular target of cancer immunotherapy [2]. Recently, PD-L1 secreted forms (soluble and vesicular) have been identified, too. They derive from alternative splicing or surface protein shedding and are able to potentiate the immunoregulatory message of membrane-bound PD-L1 in a remote, cell contact independent manner [3]. Our studies on the lung cancer human cell line H1975 confirm the positive modulation of membrane PD-L1 by IFN-gamma, enlightened the presence of PD-L1 secreted form in vesicles from H1975 culture supernatant and provided evidence for a possible reverse signaling triggered by a recombinant soluble PD1 on PD-L1 expressed by H1975 cells. Moreover, the analysis of a wide population of patients affected by NSCLC revealed the absence of correlation between the histological expression of PD-L1 in surgical tissue samples and the concentration of soluble PD-L1 measured in serum of the same individuals. This observation suggests that different cell mechanisms and/or different cell sources could contribute to the soluble form of the immune regulatory ligand PD-L1. References [1] Dong H. et al. Nat Med. 5(12):1365-9, 1999. [2] Gridelli C. et al. Transl Lung Cancer Res. 6(3):373-386, 2017. [3] Wang L. et al. Oncotarget. 6(38):41228-36, 2015.