无容量
外周血单个核细胞
提吉特
免疫系统
免疫学
免疫检查点
白色念珠菌
医学
背景(考古学)
癌症
流式细胞术
T细胞
肿瘤浸润淋巴细胞
淋巴细胞
免疫疗法
内科学
生物
体外
微生物学
古生物学
生物化学
作者
Sibylle C. Mellinghoff,Martin Thelen,Christiane Bruns,María García-Márquez,Pia Hartmann,Tatjana Lammertz,Jonas Lehmann,Angela Nowag,Jannik Stemler,Kerstin Wennhold,Oliver A. Cornely,Michael S. von Bergwelt‐Baildon,Hans Schlößer
标识
DOI:10.1016/j.jinf.2021.12.009
摘要
Recent data imply that strengthening host immunity by checkpoint inhibition improves outcome in invasive fungal infections (IFI), particularly in candidiasis.To assess T-cell exhaustion in this context, we compared peripheral blood mononuclear cells (PBMCs) and serum samples of patients with invasive Candida albicans infection (IC, n = 21) to PBMCs or tumor-infiltrating lymphocytes (TILs) from cancer patients (n = 14) and PBMCs of healthy controls (n = 20). Type and differentiation of lymphocytes and expression of 29 immune-regulatory molecules were analyzed by flow cytometry. C. albicans specific responses were assessed by FluoroSpot (n = 8) and antibody measurement (n = 14).Fractions and phenotypes of lymphocyte subsets in PBMCs of IC patients were similar compared to PBMCs of controls, while they were different in TILs. PBMCs of patients with IC showed increased expression of immune-checkpoint molecules. The pattern of upregulated molecules was similar to TILs, but not present in PBMCs of control cancer patients. Fractions of T-cells expressing PD-1 and TIGIT were higher in IC patients that died. FluoroSpot analysis showed a Candida-specific IFN-y or IL-2 response in 5/8 patients, enhanced by addition of nivolumab in vitro.Together with preclinical data and preliminary evidence of clinical efficacy in mucormycosis, our results support clinical evaluation of immune-checkpoint inhibition in IFI treatment.NCT04533087; retrospectively registered on August 31, 2020.
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