Abstract
Helicobacter-induced chronic inflammation and immune disorders are closely associated with the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Myeloid-derived suppressor cells (MDSCs) exhibit strong immunosuppressive properties and promote the growth of various solid tumors. However, the role of MDSCs in the development of MALT lymphoma has not been elucidated so far. We detected significant infiltration and enrichment of MDSCs in patients with MALT lymphoma, as well in Helicobacter felis-infected mouse model of gastric MALT lymphoma. In addition, the expression of arginase-1 and inducible nitric oxide synthase was significantly elevated both in gastric MALT lymphoma tissues and H. felis-infected stomach. Persistent H. felis infection closely reproduced the development of gastric MALT lymphoma and was accompanied by increased numbers of γδT17 cells. Accumulation of γδT17 cells was also validated in the human gastric MALT lymphoma tissues. Furthermore, the elevated cytokines interleukin-23 and interleukin-1β, as well as chemokines CCL20/CCR6, may be involved in the accumulation of γδT17 cells and the subsequent immunosuppression. These findings highlight the role of MDSCs and γδT17 cells in immune dysregulation during gastric MALT lymphoma development and their potential as therapeutic targets.
Highlights
Extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) accounts for 7–8% of all newly diagnosed lymphomas, of which gastric MALT lymphoma is the most common [1]
Myeloid-derived suppressor cells (MDSCs) were enriched in the gastric MALT lymphoma biopsies (Figures 1C,D), which correlated with significant upregulation of arginase 1 (Arg-1) and inducible nitric oxide synthase (iNOS) compared to paired normal gastric tissues (Figures 1E,F)
Since Arg-1/iNOS overexpression is a key mechanism through which MDSCs mediate local immune suppression [9,10,11], it is likely involved in creating an immunosuppressive MALT lymphoma microenvironment as well
Summary
Extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) accounts for 7–8% of all newly diagnosed lymphomas, of which gastric MALT lymphoma is the most common [1]. 90% of the gastric MALT lymphoma cases are associated with Helicobacter pylori infection [2,3,4]. Gastric MALT lymphoma is a typical model of chronic inflammation-induced gastric tumor development [5], it is essential to dissect its underlying immune mechanisms. Human MDSCs are commonly defined as CD11b+CD33+ and lack mature myeloid and lymphoid markers, as well as major histocompatibility complex class II molecule human leukocyte antigen DR isotype [7, 8]. Murine MDSCs are characterized by the myeloid-cell lineage differentiation antigens Gr-1
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