Accumulation of circulating myeloid-derived suppressor cell subsets: predicting poor clinical efficacy and prognosis through T cell suppression in non-Hodgkin's lymphoma

Author:

Pu Lian-Fang12ORCID,Li Man-Man3,Feng Xiang-Jiang12,Zhang Tun12,Hu Lin-Hui12,Zheng Hui-Min12,Charwudzi Alice12,Ding Yang-Yang12,Liu Jun12,Liu Ze-Lin12,Xiong Shu-Dao124

Affiliation:

1. Hematological Lab, The Second Affiliated Hospital of Anhui Medical University , Hefei 230601, Anhui , People's Republic of China

2. Department of Hematology, The Second Affiliated Hospital of Anhui Medical University , Hefei 230601, Anhui , People's Republic of China

3. Department of Hematology and Oncology, Minhang Hospital, Fudan University , Shanghai 201199 , People's Republic of China

4. Research Center for Translational Medicine, The Second Hospital of Anhui Medical University , Hefei 230601, Anhui , People's Republic of China

Abstract

Abstract Myeloid-derived suppressor cells (MDSCs) are implicated in the regulation of immune responses closely associated with poor clinical outcomes in cancer. However, the MDSC subtypes in non-Hodgkin's lymphoma (NHL) have not been systematically investigated. So, we investigated the percentage of MDSC subsets in 78 newly diagnosed NHL patients by flow cytometry. The results showed that all MDSC subsets increased in NHL patients compared with healthy donors. Notably, MDSCs, monocytic MDSCs, and CD14 + CD66b + MDSCs significantly increased in NHL patients compared with those with lymphadenitis donors. polymorphonuclear MDSCs (PMN-MDSCs), early-stage MDSCs (e-MDSCs), and the International Prognostic Index were independent risk factors for poor clinical efficacy and were involved in constructing the nomogram for predicting clinical efficacy. Progression-free survival (PFS) was significantly shorter in patients with high level of MDSC subsets, and PMN-MDSCs emerged as an independent prognostic factor for PFS. PMN-MDSCs, e-MDSCs, and the International Prognostic Index were involved in constructing the nomogram for predicting PFS. Patients with a higher percentage of MDSCs, PMN-MDSCs, e-MDSCs, and CD14 + CD66b + MDSCs experienced a shorter overall survival compared with those with lower percentages. In addition, research on mechanisms found that T cell function was suppressed and mediated by the expansion of MDSCs via involving arginase-1 and interleukin-10 in vitro and in vivo. In conclusion, our study demonstrates that the increased circulating MDSC subsets predict poor clinical efficacy and prognosis in NHL, potentially involving T cell suppression through MDSC subset expansion. These findings indicate the potential of MDSC subsets as comprehensive diagnostic, prognostic biomarkers, and therapeutic targets for NHL.

Funder

Key Research and Development Plan of Anhui Province, China

Foundation of Anhui Medical University

Basic and Clinical Cooperative Research Promotion Plan of Anhui Medical University

National Science Foundation of China

Higher School of Anhui Provincial Natural Science Research Major Project

Publisher

Oxford University Press (OUP)

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