 Targeting myeloid-derived suppressor cells promotes antiparasitic T-cell immunity and enhances the efficacy of PD-1 blockadeChuanshan Zhang (),
Hui Wang,
Tuerganaili Aji,
Zhide Li,
Yinshi Li,
Abidan Ainiwaer,
Zibigu Rousu,
Jing Li,
Maolin Wang,
Bingqing Deng,
Adilai Duolikun,
Xuejiao Kang,
Xuran Zheng,
Qian Yu,
Yingmei Shao,
Wenbao Zhang,
Dominique A. Vuitton,
Zhigang Tian,
Haoyu Sun () and
Hao Wen ()
Nature Communications, 2024, vol. 15, issue 1, 1-19 Abstract: Abstract Immune exhaustion corresponds to a loss of effector function of T cells that associates with cancer or chronic infection. Here, our objective was to decipher the mechanisms involved in the immune suppression of myeloid-derived suppressor cells (MDSCs) and to explore the potential to target these cells for immunotherapy to enhance checkpoint blockade efficacy in a chronic parasite infection. We demonstrated that programmed cell-death-1 (PD-1) expression was significantly upregulated and associated with T-cell dysfunction in advanced alveolar echinococcosis (AE) patients and in Echinococcus multilocularis-infected mice. PD-1 blockade ex vivo failed to reverse AE patients’ peripheral blood T-cell dysfunction. PD-1/PD-L1 blockade or PD-1 deficiency had no significant effects on metacestode in mouse model. This was due to the inhibitory capacities of immunosuppressive granulocytic MDSCs (G-MDSCs), especially in the liver surrounding the parasite pseudotumor. MDSCs suppressed T-cell function in vitro in an indoleamine 2, 3 dioxygenase 1 (IDO1)-dependent manner. Although depleting MDSCs alone restored T-cell effector functions and led to some limitation of disease progression in E. multilocularis-infected mice, combination with PD-1 blockade was better to induce antiparasitic efficacy. Our findings provide preclinical evidence in support of targeting MDSC or combining such an approach with checkpoint blockade in patients with advanced AE. Date: 2024 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50754-7 Ordering information: This journal article can be ordered from DOI: 10.1038/s41467-024-50754-7 Access Statistics for this article Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie More articles in Nature Communications from Nature |
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