Protective activity of programmed cell death protein 1 blockade and synergy with caspofungin in a murine invasive pulmonary aspergillosis model

Sebastian Wurster, Prema Robinson, Nathaniel D. Albert, Jeffrey J. Tarrand, Marisa Goff, Muthulekha Swamydas, Jean K. Lim, Michail S. Lionakis, Dimitrios P. Kontoyiannis

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Pharmacological immune checkpoint blockade has revolutionized oncological therapies, and its remarkable success has sparked interest in expanding checkpoint inhibitor therapy in infectious diseases. Herein, we evaluated the efficacy of programmed cell death protein 1 (PD-1) blockade in a murine invasive pulmonary aspergillosis model. We found that, compared with isotype-treated infected control mice, anti-PD-1-treated mice had improved survival, reduced fungal burden, increased lung concentrations of proinflammatory cytokines and neutrophil-attracting chemokines, and enhanced pulmonary leukocyte accumulation. Furthermore, combined treatment with anti-PD-1 and caspofungin resulted in a significant survival benefit compared with caspofungin or anti-PD-1 therapy alone, indicating a synergistic effect between PD-1 inhibitors and immunomodulatory antifungal agents.

Original languageEnglish (US)
Pages (from-to)989-994
Number of pages6
JournalJournal of Infectious Diseases
Volume222
Issue number6
DOIs
StatePublished - Sep 15 2020

Keywords

  • Antifungals
  • Checkpoint inhibitors
  • Cytokines
  • Immunotherapy
  • Invasive aspergillosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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