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

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. (C) 2017 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.