Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jan 15, 2022; 14(1): 153-162
Published online Jan 15, 2022. doi: 10.4251/wjgo.v14.i1.153
Impact of the microenvironment on the pathogenesis of mucosa-associated lymphoid tissue lymphomas
Barbara Uhl, Katharina T Prochazka, Karoline Fechter, Katrin Pansy, Hildegard T Greinix, Peter Neumeister, Alexander JA Deutsch
Barbara Uhl, Katharina T Prochazka, Karoline Fechter, Katrin Pansy, Hildegard T Greinix, Peter Neumeister, Alexander JA Deutsch, Division of Hematology, Medical University of Graz, Graz 8036, Austria
Author contributions: Uhl B and Deutsch AJA drafted the work; all authors conceived the work and made substantial revisions to and critiqued the content; all authors have read and approved the final manuscript.
Conflict-of-interest statement: The authors declare no conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Alexander JA Deutsch, PhD, Research Assistant Professor, Division of Hematology, Medical University of Graz, Auenbruggerplatz 38, Graz 8036, Austria.
Received: February 25, 2021
Peer-review started: February 25, 2021
First decision: May 3, 2021
Revised: May 16, 2021
Accepted: December 9, 2021
Article in press: December 9, 2021
Published online: January 15, 2022

Approximately 8% of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphomas of mucosa-associated lymphoid tissue (MALT), also known as MALT lymphomas. These arise at a wide range of different extranodal sites, with most cases affecting the stomach, the lung, the ocular adnexa and the thyroid. The small intestine is involved in a lower percentage of cases. Lymphoma growth in the early stages is associated with long-lasting chronic inflammation provoked by bacterial infections (e.g., Helicobacter pylori or Chlamydia psittaci infections) or autoimmune conditions (e.g., Sjögren’s syndrome or Hashimoto thyroiditis). While these inflammatory processes trigger lymphoma cell proliferation and/or survival, they also shape the microenvironment. Thus, activated immune cells are actively recruited to the lymphoma, resulting in either direct lymphoma cell stimulation via surface receptor interactions and/or indirect lymphoma cell stimulation via secretion of soluble factors like cytokines. In addition, chronic inflammatory conditions cause the acquisition of genetic alterations resulting in autonomous lymphoma cell growth. Recently, novel agents targeting the microenvironment have been developed and clinically tested in MALT lymphomas as well as other lymphoid malignancies. In this review, we aim to describe the composition of the microenvironment of MALT lymphoma, the interaction of activated immune cells with lymphoma cells and novel therapeutic approaches in MALT lymphomas using immunomodulatory and/or microenvironment-targeting agents.

Keywords: Mucosa-associated lymphoid tissue lymphoma, Tumor microenvironment, Microenvironment, Helicobacter pylori, Activated immune cells

Core Tip: This review summarizes and discusses the major findings in extranodal mucosa-associated lymphoid tissue lymphomas with a focus on the microenvironment. It describes how long-lasting chronic inflammatory processes promote the growth of malignant cells, which can be directly mediated by bacteria and/or interaction with activated immune cells. In addition, major genetic alterations are summarized, and models of how these might be acquired are discussed. Finally, novel therapies targeting the microenvironment are described.