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Immune checkpoint blockade in experimental bacterial infections
Nicole L Henriksen1, Peter Ø Jensen2, Louise K Jensen1
1Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark.
Abstract:
Immune checkpoint inhibitors designed to reinvigorate immune responses suppressed by cancer cells have revolutionized cancer therapy. Similarities in immune dysregulation between cancer and infectious diseases have prompted investigations into the role of immune checkpoints in infectious diseases, including the therapeutic potential of immune checkpoint blockade and drug repurposing. While most research has centered around viral infections, data for bacterial infections are emerging. This systematic review reports on the in vivo effect of immune checkpoint blockade on bacterial burden and selected immune responses in preclinical studies of bacterial infection, aiming to assess if there could be a rationale for using immunotherapy for bacterial infections. Of the 42 analyzed studies, immune checkpoint blockade reduced the bacterial burden in 60% of studies, had no effect in 28% and increased the bacterial burden in 12%. Findings suggest that the effect of immune checkpoint blockade on bacterial burden is context-dependent and in part relates to the pathogen. Further preclinical research is required to understand how the therapeutic effect of immune checkpoint blockade is mediated in different bacterial infections, and if immune checkpoint blockade can be used as an adjuvant to conventional infection management strategies.
Insights
Immune checkpoint blockade shows potential for bacterial infections, reducing bacterial burden in 60% of preclinical studies. Further research is needed to optimize immunotherapy strategies for managing bacterial infections.
Area of Science:
- Immunology
- Infectious Diseases
- Cancer Therapy
Background:
- Immune checkpoint inhibitors (ICIs) have transformed cancer treatment by restoring anti-tumor immunity.
- Shared mechanisms of immune dysregulation in cancer and infections suggest ICIs may be relevant for infectious diseases.
- While viral infections have been studied, research on ICIs in bacterial infections is nascent.
Purpose of the Study:
- To systematically review preclinical studies on the in vivo effects of immune checkpoint blockade (ICB) in bacterial infections.
- To assess the impact of ICB on bacterial burden and immune responses.
- To determine the rationale for using immunotherapy in bacterial infections.
Main Methods:
- Systematic review of preclinical studies investigating ICB in bacterial infections.
- Analysis of reported effects on bacterial burden and immune responses.
- Categorization of study outcomes based on ICB efficacy.
Main Results:
- Immune checkpoint blockade reduced bacterial burden in 60% of the 42 analyzed studies.
- No effect on bacterial burden was observed in 28% of studies.
- An increase in bacterial burden occurred in 12% of studies, indicating context-dependent effects.
Conclusions:
- The efficacy of immune checkpoint blockade in bacterial infections is pathogen- and context-dependent.
- Further preclinical investigation is crucial to elucidate the mechanisms of ICB in bacterial infections.
- ICB may hold potential as an adjunctive therapy to conventional strategies for managing bacterial infections.
