title: CD13hiNeutrophil-like myeloid-derived suppressor cells exert immune suppression through Arginase 1 expression in pancreatic ductal adenocarcinoma.
abstract: Perineural invasion and immunosuppressive tumor microenvironment are the distinct features of pancreatic ductal adenocarcinoma (PDAC). Heterogeneous myeloid-derived suppressor cells (MDSCs) are potent suppressors of antitumor immunity, posing obstacles for cancer immunotherapy. Increasing evidences have demonstrated the accumulation of MDSCs in PDAC patients. However, the role of MDSCs in perineural invasion of PDAC and the existence of novel MDSC subsets during PDAC remain unclear. This study found that lymphocytic perineural cuffs were frequently present in chronic pancreatitis (CP) tissues and adjacent non-neoplastic pancreatic tissues (ANPTs), but not in PDAC with perineural invasion. Meanwhile, we found that neutrophil-like MDSCs (nMDSCs), but not monocyte-like MDSCs (mMDSCs), were significantly increased in PBMCs and tumor tissues of PDAC patients. Further observation identified two distinct subsets of nMDSCs, CD13hiand CD13lownMDSCs in PDAC patients, which have not been reported previously. Despite a similar morphology, CD13hinMDSCs expressed higher levels of CD11b, CD33, CD16 and arginase 1 but lower levels of CD66b than CD13lownMDSCs. Importantly, CD13hiMDSCs, compared with CD13lownMDSCs, more effectively suppressed alloreactive T cell responses via an arginase-1-related mechanism. After tumor resection, the circulating CD13hinMDSCs were decreased markedly. PDAC patients with more CD13hinMDSCs had a shorter overall survival than those with less CD13hinMDSCs. To conclude, we identified two novel MDSC subsets with different characteristics and functions in PDAC, demonstrated the association of the two MDSC subsets with cancer progression, and explored their roles in perineural invasion and immune escape of PDAC.
authors.affiliation: Department of Pathology, Changhai Hospital, Second Military Medical University , Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Second Military Medical University , Shanghai, China.
authors.forename: Xiongfei
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Pathology, Changhai Hospital, Second Military Medical University , Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Pathology, Changhai Hospital, Second Military Medical University , Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pathology, Changhai Hospital, Second Military Medical University , Shanghai, China.
authors.forename: Danghui
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Pathology, Changhai Hospital, Second Military Medical University , Shanghai, China.
authors.forename: Chenyan
authors.initials: C
authors.lastname: Zhao
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University , Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University , Shanghai, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University , Shanghai, China.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Pathology, Changhai Hospital, Second Military Medical University , Shanghai, China.
authors.forename: Guiling
authors.initials: G
authors.lastname: Ding
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University , Shanghai, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Jin
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Harvard Medical University , Boston, MA, USA.
authors.forename: Chin-Lee
authors.initials: CL
authors.lastname: Wu
authors.affiliation: Department of Pathology, Changhai Hospital, Second Military Medical University , Shanghai, China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Zhu
keywords: Immune escape; myeloid-derived suppressor cells; pancreatic ductal adenocarcinoma; tumor microenvironment