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Is it possible to overcome antiapoptotic API2/MALT1 events in tumor B-cells by influencing Tregs in MALT lymphoma?

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) comprises approximately 50% of primary gastric lymphoma. Proliferation of tumor cells infected with Helicobacter pylori is facilitated by the presence of T cells activated by H. pylori antigens. Unlike the majority of MALT lymphomas, tumors bearing the t(11 ; 18)(q21 ; q21) resulting in production of a chimeric protein API2/MALT1 are often resistant to H. pylori eradication therapy, and require more aggressive therapeutic approach including chemotherapy. The authors hypothesize that a subset of patients with translocation- positive MALT lymphoma might benefit from a novel therapeutic approach that would address intercellular communication pathways between various cell types in the tumor microenvironment. A subset of T cells called regulatory T cells (Tregs) are one of the major immunomodulators of antitumor response mechanisms. There are several potential tools that could have a substantial impact on this particular T cell population, such as interleukin (IL)-15, indoleamine 2, 3- dioxigenase (IDO), anti-CD25 antibodies. Introducing some of these components into treatment protocols for patients with API2/MALT1 translocation-positive MALT lymphomas might also prove to be benefitial for other lymphomas with increased number of intratumoral Tregs.

MALT lymphoma; T regs; Helicobacter pylori; API2/MALT1

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