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Tumor-associated macrophages as major source of APRIL in gastric MALT lymphoma
Fabio Munari1, Silvia Lonardi, Marco A Cassatella
1Venetian Institute of Molecular Medicine, Padua, Italy.
Abstract:
Lymphoid hyperplasia of gastric mucosa associated with Helicobacter pylori (HP) infection represents a preneoplastic condition of the mucosa associated lymphoid tissue (MALT), which may evolve to a B-cell lymphoma. While it is well established that the initial neoplastic proliferation of B cells is antigen-driven and dependent on the helper activity of HP-specific T cells, it needs to be elucidated which cytokine or soluble factor(s) promote B-cell activation and lymphomagenesis. Herein, we originally report that gastric MALT lymphoma express high levels of a proliferation inducing ligand (APRIL), a novel cytokine crucial in sustaining B-cell proliferation. By immunohistochemistry, we demonstrate that APRIL is produced almost exclusively by gastric lymphoma-infiltrating macrophages located in close proximity to neoplastic B cells. We also show that macrophages produce APRIL on direct stimulation with both HP and HP-specific T cells. Collectively, our results represent the first evidence for an involvement of APRIL in gastric MALT lymphoma development in HP-infected patients.
Insights
Helicobacter pylori (HP) infection can lead to gastric MALT lymphoma. This study found that macrophages produce APRIL, a cytokine that sustains B-cell proliferation, promoting HP-associated gastric MALT lymphoma development.
Area of Science:
- Gastroenterology
- Immunology
- Oncology
Background:
- Helicobacter pylori (HP) infection causes gastric lymphoid hyperplasia, a preneoplastic condition of mucosa-associated lymphoid tissue (MALT).
- This condition can progress to B-cell lymphoma, driven by antigen-specific B cells and HP-specific T cells.
- The specific cytokines promoting B-cell activation and lymphomagenesis in this context remain unclear.
Purpose of the Study:
- To investigate the role of cytokines in Helicobacter pylori-associated gastric MALT lymphoma development.
- To identify novel soluble factors involved in B-cell activation and lymphomagenesis within gastric MALT lymphoma.
Main Methods:
- Immunohistochemistry was used to detect the expression of proliferation-inducing ligand (APRIL) in gastric MALT lymphoma tissues.
- The study examined APRIL production by macrophages in response to direct stimulation with HP and HP-specific T cells.
Main Results:
- Gastric MALT lymphomas exhibited high levels of APRIL, a cytokine essential for B-cell proliferation.
- APRIL was predominantly produced by macrophages infiltrating the gastric lymphoma, situated near neoplastic B cells.
- Macrophage production of APRIL was induced by direct stimulation with both HP and HP-specific T cells.
Conclusions:
- This study provides the first evidence implicating APRIL in the development of gastric MALT lymphoma in HP-infected patients.
- APRIL, produced by tumor-infiltrating macrophages, plays a crucial role in sustaining the proliferation of neoplastic B cells in HP-associated gastric MALT lymphoma.