Next Article in Journal
Dasatinib Treatment Increases Sensitivity to c-Met Inhibition in Triple-Negative Breast Cancer Cells
Previous Article in Journal
Frequent Occurrence of NRAS and BRAF Mutations in Human Acral Naevi
Previous Article in Special Issue
The Association between Salt and Potential Mediators of the Gastric Precancerous Process
Article Menu

Export Article

Open AccessReview
Cancers 2019, 11(4), 547; https://doi.org/10.3390/cancers11040547

Novel Insights of Lymphomagenesis of Helicobacter pylori-Dependent Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

1
Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan
2
Cancer Research Center, National Taiwan University College of Medicine, Taipei 100, Taiwan
3
Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei 100, Taiwan
4
National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei 106, Taiwan
5
Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan
6
Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan
7
National Institute of Cancer Research, National Health Research Institutes, Tainan 704, Taiwan
8
Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
9
Department of Internal Medicine, National Cheng-Kung University Hospital, Tainan 704, Taiwan
*
Author to whom correspondence should be addressed.
Received: 24 March 2019 / Revised: 9 April 2019 / Accepted: 12 April 2019 / Published: 17 April 2019
(This article belongs to the Special Issue Helicobacter pylori Associated Cancer)
  |  
PDF [1091 KB, uploaded 17 April 2019]
  |     |  

Abstract

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is the most common subtype of gastric lymphoma. Most gastric MALT lymphomas are characterized by their association with the Helicobacter pylori (HP) infection and are cured by first-line HP eradication therapy (HPE). Several studies have been conducted to investigate why most gastric MALT lymphomas remain localized, are dependent on HP infection, and show HP-specific intratumoral T-cells (e.g., CD40-mediated signaling, T-helper-2 (Th2)-type cytokines, chemokines, costimulatory molecules, and FOXP3+ regulatory T-cells) and their communication with B-cells. Furthermore, the reason why the antigen stimuli of these intratumoral T-cells with tonic B-cell receptor signaling promote lymphomagenesis of gastric MALT lymphoma has also been investigated. In addition to the aforementioned mechanisms, it has been demonstrated that the translocated HP cytotoxin-associated gene A (CagA) can promote B-cell proliferation through the activation of Src homology-2 domain-containing phosphatase (SHP-2) phosphorylation-dependent signaling, extracellular-signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), B-cell lymphoma (Bcl)-2, and Bcl-xL. Furthermore, the expression of CagA and these CagA-signaling molecules is closely associated with the HP-dependence of gastric MALT lymphomas (completely respond to first-line HPE). In this article, we summarize evidence of the classical theory of HP-reactive T-cells and the new paradigm of direct interaction between HP and B-cells that contributes to the HP-dependent lymphomagenesis of gastric MALT lymphomas. Although the role of first-line HPE in the treatment of HP-negative gastric MALT lymphoma remains uncertain, several case series suggest that a proportion of HP-negative gastric MALT lymphomas remains antibiotic-responsive and is cured by HPE. Considering the complicated interaction between microbiomes and the genome/epigenome, further studies on the precise mechanisms of HP- and other bacteria-directed lymphomagenesis in antibiotic-responsive gastric MALT lymphomas are warranted. View Full-Text
Keywords: MALT lymphoma; Helicobater pylori; T-cell; Tregs; CagA MALT lymphoma; Helicobater pylori; T-cell; Tregs; CagA
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Kuo, S.-H.; Wu, M.-S.; Yeh, K.-H.; Lin, C.-W.; Hsu, P.-N.; Chen, L.-T.; Cheng, A.-L. Novel Insights of Lymphomagenesis of Helicobacter pylori-Dependent Gastric Mucosa-Associated Lymphoid Tissue Lymphoma. Cancers 2019, 11, 547.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top