ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicHarnessing Macrophage Modulation: Advancing Hematologic Cancer Treatment StrategiesView all 5 articles
In the diffuse large B-cell lymphoma microenvironment, autophagy genes are upregulated in pro-inflammatory macrophages and linked to BCL2 overexpression
Provisionally accepted
- 1Department of Surgical Pathology. University Hospital of Navarra, Navarra, Spain
- 2Biogipuzkoa Health Research Institute, San Sebastian, Spain
- 3Icahn School of Medicine at Mount Sinai, New York, United States
- 4IKERBASQUE Basque Foundation for Science, Bilbao, Spain
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Diffuse large B-cell lymphoma (DLBCL) is one of the most frequent B-cell non-Hodgkin lymphoma types. It is characterized by a complex immune microenvironment, rich in macrophages (innate immunity cells), and high aggressiveness. DLBCL cells might respond to the increased energy demand by enhancing key metabolic processes, such as autophagy in which damaged cell constituents and debris are sequestered/removed for recycling. Here, we investigated the autophagy gene expression profile in DLBCL and in non-tumor controls using publicly available gene expression datasets and a substantial cohort of patients' tissue samples. For the first time, we describe in the DLBCL microenvironment, a differential autophagy gene expression profile characterized by overexpression of BCL2 (anti-apoptotic factor) in M1 pro-inflammatory macrophages compared with M2 immuno-suppressive macrophages. Moreover, the expression levels of CD86 (M1 macrophage marker) and CSF1R (M2 macrophage marker) were positively correlated with those of BECN1 (autophagy regulator) and BCL2 (only CD86) that were in turn correlated with MTOR expression in tumor B cells and in the CD86+ macrophage subtype. We confirmed these results by immunohistochemistry and immunofluorescence analyses of DLBCL and non-tumor tissue samples. Our finding of an autophagy-related pro-inflammatory signature highlights the crucial role of autophagy in the DLBCL immune microenvironment and suggests its potential as a therapeutic target.
Keywords: Lymphoma, Macrophages, Inflammation, Autophagy, BCL2
Received: 30 Jul 2025; Accepted: 11 Nov 2025.
Copyright: © 2025 Resanoa, Delgado, Rodiño, Villar, Aiastui and Braza. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mounia S Braza, msbpro25@protonmail.com
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