Diffuse large B-cell lymphoma (DLBCL), the most common aggressive non-Hodgkin lymphoma, frequently involves the gastrointestinal tract—a site characterized by chronic inflammation and unique microbiota that fuel aerobic glycolysis in tumor cells. This metabolic reprogramming not only drives rapid proliferation but also reshapes the local immune microenvironment, promoting immune evasion. Yet, the molecular links between glycolysis and immunity in this specific subtype remain poorly understood.
A new study published in Pathology Research addresses this gap. Led by Yubing Zhu and colleagues from the Tumor Hospital Affiliated to Xinjiang Medical University, the research investigates ENO1—a key rate-limiting glycolytic enzyme—in 95 newly diagnosed PGI-DLBCL patients. Through immunohistochemistry, multiplex immunofluorescence, and peripheral blood analysis, the team systematically examined ENO1 expression, tumor-infiltrating lymphocyte (TIL) profiles, macrophage polarization, and LMR.
The findings are striking. High ENO1 expression was significantly associated with:
Increased macrophage infiltration and a marked shift toward M2 polarization (elevated M2/total macrophage ratio and M2/M1 ratio);
Lower LMR, which in turn correlated with reduced CD8⁺ T-cell infiltration;
Shorter overall survival, confirmed by multivariate Cox regression analysis, which identified high ENO1 expression as an independent adverse prognostic factor (HR = 9.032, P = 0.002), while LMR and CD4⁺ T-cell infiltration emerged as protective factors.
Mechanistically, the study suggests that ENO1-driven glycolysis may create a lactate-dominated, acidic tumor microenvironment that drives macrophages toward the immunosuppressive M2 phenotype while dampening T-cell activation—a phenomenon increasingly recognized across multiple cancers. Importantly, the correlation between ENO1 and LMR hints at an intrinsic link between local metabolic reprogramming and systemic immune-inflammatory balance, though the precise biological mechanisms warrant further investigation.
The study also acknowledges its limitations: single-center retrospective design, incomplete clinical data (e.g., treatment regimens, IPI scores), and the need for larger multicenter validation and mechanistic experiments. Nevertheless, these findings position ENO1 as a promising prognostic biomarker and a potential therapeutic target in PGI-DLBCL.
DOI:10.2738/PR.2026.0002