International immunopharmacology · 2022
Abnormal immune function of MDSC and NK cells from chronic phase CML patients restores with tyrosine kinase inhibitors.
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Hong Yunguang, Wen Ruiting, Wu Guocai, Li Shi, Liu Wenxin, Chen Zhanghui, Yang Zhigang
Аннотация
BACKGROUND: Myeloid-derived suppressor cell (MDSC) -mediated immune suppression, and natural killer (NK) and/or T cell-mediated immune responses play important roles in Chronic myeloid leukemia (CML). However, detailed regulation mechanisms of these immune cells in CML have not been fully elucidated.
METHODS: The proportion of MDSCs and effector NK cells in newly diagnosed CML patients, patients during TKI treatment, and healthy donors (HD) were detected using flow cytometry. Serum levels and mRNA expression of Arg1 and iNOS in newly diagnosed CML patients, patients during TKI treatment, and HD were measured by ELISA and qPCR, respectively. Effect of CML serum or peripheral blood mononuclear cells (PBMCs) on HD derived CD3+ T cell proliferation was evaluated by CFSE-labeled HD CD3+ T cells co-cultured with PBMCs and serum from CML patients. Effect of CML serum on NK cells killing activity was evaluated via detecting apoptosis of K562 cells.
RESULTS: Proportion of Gr-MDSCs and the serum levels of Arg1 and iNOS were significantly increased in patients at diagnosis, and reduced following TKI treatment. However, the proportion of effector NK cells were decreased in patients at diagnosis, and increased following TKI treatment. Serum and PBMC from CML patients suppressed HD derived T cell proliferation in vitro. Additionally, serum from CML patients enhanced HD derived NK cell killing activity in vitro, while the addition of Arg1 inhibitor to CML serum suppressed this phenomenon.
CONCLUSIONS: Gr-MDSCs and effector NK cells play an important role in the pathogenesis of CML, inhibiting the function of MDSC and restoring the function of NK cells is expected to be a therapeutic strategy for CML.
METHODS: The proportion of MDSCs and effector NK cells in newly diagnosed CML patients, patients during TKI treatment, and healthy donors (HD) were detected using flow cytometry. Serum levels and mRNA expression of Arg1 and iNOS in newly diagnosed CML patients, patients during TKI treatment, and HD were measured by ELISA and qPCR, respectively. Effect of CML serum or peripheral blood mononuclear cells (PBMCs) on HD derived CD3+ T cell proliferation was evaluated by CFSE-labeled HD CD3+ T cells co-cultured with PBMCs and serum from CML patients. Effect of CML serum on NK cells killing activity was evaluated via detecting apoptosis of K562 cells.
RESULTS: Proportion of Gr-MDSCs and the serum levels of Arg1 and iNOS were significantly increased in patients at diagnosis, and reduced following TKI treatment. However, the proportion of effector NK cells were decreased in patients at diagnosis, and increased following TKI treatment. Serum and PBMC from CML patients suppressed HD derived T cell proliferation in vitro. Additionally, serum from CML patients enhanced HD derived NK cell killing activity in vitro, while the addition of Arg1 inhibitor to CML serum suppressed this phenomenon.
CONCLUSIONS: Gr-MDSCs and effector NK cells play an important role in the pathogenesis of CML, inhibiting the function of MDSC and restoring the function of NK cells is expected to be a therapeutic strategy for CML.