Protective Activity of Programmed Cell Death Protein 1 Blockade and Synergy With Caspofungin in a Murine Invasive Pulmonary Aspergillosis Model

程序性细胞死亡蛋白 1 阻断剂的保护活性及其与卡泊芬净的协同作用在小鼠侵袭性肺曲霉病模型中

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

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.

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