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Leo I. Gordon, MD, FACP


Does Microenvironment Impact the Pathogenesis of MALT Lymphomas?

By: Sarah Campen, PharmD
Posted: Monday, May 9, 2022

According to a review published in the World Journal of Gastrointestinal Oncology, the pathogenesis of extranodal mucosa-associated lymphoid tissue (MALT) lymphomas seems to be dependent on microenvironmental factors. Alexander J.A. Deutsch, PhD, of the Medical University of Graz, Austria, and colleagues explained that the development of MALT lymphomas is often the result of long-lasting chronic inflammation stimulated by bacterial infections, usually Helicobacter pylori, or autoimmune conditions such as primary Sjögren’s syndrome and Hashimoto thyroiditis. “While these inflammatory processes trigger lymphoma cell proliferation and/or survival, they also shape the microenvironment,” stated the authors.

Prolonged inflammation is the trigger of a multistep process in the evolution of MALT lymphomas. First, regulatory T cells are activated and suppress the immune response by influencing cytotoxic T cells. Next, eosinophils and macrophages express a proliferation-inducing ligand and B-cell–activating factor, supporting lymphomagenesis. Finally, T helper cells and their cytokines—such as interleukin 4 (IL-4), IL-5, and IL-10—promote the growth and differentiation of lymphoma cells.

In MALT lymphomas, recurrent chromosomal aberrations have been identified. Inflammatory processes may also lead to the acquisition of further genetic alterations, resulting in autonomous lymphoma cell growth, independent of chronic infection or autoimmune disorders.

Because MALT lymphomas cause B-cell proliferation both directly and indirectly by activation of immune cells, multiple potential targets for new immunomodulatory treatments exist. Several agents have been developed in recent years—including Bruton’s tyrosine kinase inhibitors, bortezomib, and immunomodulatory drugs—that target the interaction of immune cells of the microenvironment with lymphoma cells, indicating that the basis for novel therapeutic strategies is available.

Disclosure: The authors reported no conflicts of interest.

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