Increased myeloid-derived suppressor cells in patients with myelodysplastic syndromes suppress CD8+ T lymphocyte function through the STAT3-ARG1 pathway.

Abstract:

:MDSCs, which are defined as a kind of negatively regulatory cells, could suppress T cell immune response in many tumor-bearing animal models and cancer patients. We supposed that MDSCs also contributed to the impaired antitumor immunity in MDS. Here we demonstrated that STAT3-ARG1 pathway could be a critical signal transduction pathway that regulated MDSCs-mediated immunosuppression. Increased MDSCs was revealed in MDS patients when compared to healthy controls. Especially, MDSCs performed higher activated STAT3 and CCR2 expression in high-risk MDS patients. The CCL2 and IL-6 levels in MDS patients were also higher than in healthy controls, which could drive recruitment and activation of MDSCs. Meanwhile, lower expression levels of CD3ζ chain, perforin and granzyme B were demonstrated in MDS patients, which were associated with downregulated activation of CD8+ T lymphocytes. The results were supported by the decreased perforin, granzyme B and IFN-γ levels in the mixed-culture system of MDSCs and CD8+ T lymphocytes in vitro. Notably, targeting STAT3 pathway by selective inhibitor could decrease ARG1 expression in MDSCs and partially reverse the lower expression levels of effector molecules on CD8+ T lymphocytes. Therefore, this study revealed the potential STAT3-ARG1 mechanism behind MDSCs and provided a promising STAT3 targeting strategy in MDS.

journal_name

Leuk Lymphoma

journal_title

Leukemia & lymphoma

authors

Qi X,Jiang H,Liu P,Xie N,Fu R,Wang H,Liu C,Zhang T,Wang H,Shao Z

doi

10.1080/10428194.2020.1817431

subject

Has Abstract

pub_date

2021-01-01 00:00:00

pages

218-223

issue

1

eissn

1042-8194

issn

1029-2403

journal_volume

62

pub_type

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