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

Int J Infect Dis. 2017 Mar;56:221-228. doi: 10.1016/j.ijid.2017.01.028. Epub 2017 Feb 2.


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.

Keywords: Anti-PD-1; Anti-PD-L1; Cancer; Host-directed therapy; Infectious disease; T-cells.

Publication types

  • Review

MeSH terms

  • Anti-Infective Agents / therapeutic use*
  • Antibodies, Monoclonal / therapeutic use
  • CTLA-4 Antigen / antagonists & inhibitors*
  • Communicable Diseases / drug therapy*
  • Humans
  • Immunotherapy
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • T-Lymphocytes / immunology


  • Anti-Infective Agents
  • Antibodies, Monoclonal
  • CTLA-4 Antigen
  • Programmed Cell Death 1 Receptor