Anti-PD-1/PD-L1 therapy for infectious diseases: learning from the cancer paradigm

• Main Authors: Martin Rao, Davide Valentini, Ernest Dodoo, Alimuddin Zumla, Markus Maeurer
• Format: Article
• Language: English
• Published: Elsevier 2017-03-01
• Series: International Journal of Infectious Diseases
• Subjects: Anti-PD-1; Anti-PD-L1; T-cells; Cancer; Infectious disease; Host-directed therapy
• Online Access: http://www.sciencedirect.com/science/article/pii/S1201971217300310

Objectives: Immune checkpoint pathways regulate optimal host immune responses against transformed cells, induce immunological memory, and limit tissue pathology. Conversely, aberrant immune checkpoint activity signifies a poor prognosis in cancer and infectious diseases. Host-directed therapy (HDT) via immune checkpoint blockade has revolutionized cancer treatment with therapeutic implications for chronic infections, thus laying the foundation for this review. Methods: Online literature searches were performed via PubMed, PubMed Central, and Google using the keywords “immune checkpoint inhibition”; “host-directed therapy”; “T cell exhaustion”; “cancer immunotherapy”; “anti-PD-1 therapy”; “anti-PD-L1 therapy”; “chronic infections”; “antigen-specific cells”; “tuberculosis”; “malaria”; “viral infections”; “human immunodeficiency virus”; “hepatitis B virus”; “hepatitis C virus”; “cytomegalovirus” and “Epstein–Barr virus”. Search results were filtered based on relevance to the topics covered in this review. Results: The use of monoclonal antibodies directed against the antigen-experienced T-cell marker programmed cell death 1 (PD-1) and its ligand PD-L1 in the context of chronic infectious diseases is reviewed. The potential pitfalls and precautions, based on clinical experience from treating patients with cancer with PD-1/PD-L1 pathway inhibitors, are also described. Conclusions: Anti-PD-1/PD-L1 therapy holds promise as adjunctive therapy for chronic infectious diseases such as tuberculosis and HIV, and must therefore be tested in randomized clinical trials.