Anti-PD-1/PD-L1 therapy for infectious diseases: learning from the cancer paradigm.
OBJECTIVE
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.
Division of Therapeutic Immunology (TIM), Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm, Sweden.
Martin
M
Rao
Division of Therapeutic Immunology (TIM), Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm, Sweden; Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge, Stockholm, Sweden.
Davide
D
Valentini
Division of Therapeutic Immunology (TIM), Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm, Sweden; Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden.
Ernest
E
Dodoo
Division of Infection and Immunity, University College London, and NIHR Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, London, UK.
Alimuddin
A
Zumla
Division of Therapeutic Immunology (TIM), Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm, Sweden; Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge, Stockholm, Sweden. Electronic address: markus.maeurer@ki.se.
Markus
M
Maeurer
D000890:Anti-Infective Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors*; D003141:Communicable Diseases / Q000188:drug therapy*; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D013601:T-Lymphocytes / Q000276:immunology
D000890:Anti-Infective Agents; D000911:Antibodies, Monoclonal; D060908:CTLA-4 Antigen; D061026:Programmed Cell Death 1 Receptor
Anti-PD-1; Anti-PD-L1; Cancer; Host-directed therapy; Infectious disease; T-cells