PD-L1 in systemic immunity: unraveling its contribution to PD-1/PD-L1 blockade immunotherapy

The use of monoclonal antibodies targeting PD-1/PD-L1 axis completely changed anticancer treatment strategies. However, despite the significant improvement in overall survival and progression-free survival of patients undergoing these immunotherapy treatments, the only clinically accepted biomarker with some prediction capabilities for the outcome of the treatment is PD-L1 expression in tumor biopsies. Nevertheless, even when having PD-L1-positive tumors, numerous patients do not respond to these treatments. Considering the high cost of these therapies and the risk of immune-related adverse events during therapy, it is necessary to identify additional biomarkers that would facilitate stratifying patients in potential responders and non-responders before the start of immunotherapies. Here, we review the utility of PD-L1 expression not only in tumor cells but in immune system cells and their influence on the antitumor activity of immune cell subsets. ; The Oncoimmunology group is funded by Asociación Española Contra el Cáncer, (AECC PROYE16001ESCO); Instituto de Salud Carlos III, Spain, (FIS grant PI17/02119); and a 'Precipita' Crowdfunding grant (FECYT), no grant number; Government of Navarre grant (BMED 050-2019); Independent Clinical Research Projects Call (Instituto de Salud Carlos III, Spain; TRANSPOCART); Proyectos estratégicos I+D, Departamento de Industria, Gobierno de Navarra (DESCARTHES).