TY - JOUR
T1 - Protective activity of programmed cell death protein 1 blockade and synergy with caspofungin in a murine invasive pulmonary aspergillosis model
AU - Wurster, Sebastian
AU - Robinson, Prema
AU - Albert, Nathaniel D.
AU - Tarrand, Jeffrey J.
AU - Goff, Marisa
AU - Swamydas, Muthulekha
AU - Lim, Jean K.
AU - Lionakis, Michail S.
AU - Kontoyiannis, Dimitrios P.
N1 - Funding Information:
This study was supported by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (grant 5R03AI137754 to D. P. K. and support from the NIAID Division of Intramural Research to M. S. L.), the Texas 4000 for Cancer Distinguished Professorship for Cancer Research (D. P. K.), the National Cancer Institute, National Institutes of Health (Cancer Center CORE support grant 16672), and the MD Anderson Cancer Center's Division of Internal Medicine (research and quality improvement award to S. W.).
Publisher Copyright:
© Published by Oxford University Press for the Infectious Diseases Society of America 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.
PY - 2020/9/15
Y1 - 2020/9/15
N2 - 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.
AB - 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.
KW - Antifungals
KW - Checkpoint inhibitors
KW - Cytokines
KW - Immunotherapy
KW - Invasive aspergillosis
UR - http://www.scopus.com/inward/record.url?scp=85089710090&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiaa264
DO - 10.1093/infdis/jiaa264
M3 - Article
C2 - 32432714
AN - SCOPUS:85089710090
SN - 0022-1899
VL - 222
SP - 989
EP - 994
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 6
ER -