Microenvironment expression in diffuse large B-cell lymphomas

Diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin lymphoma, is recognized as a heterogeneous disease with distinct molecular subtypes derived from different stages of B-cell differentiation. The contribution of the tumor microenvironment to the pathogenesis and tumor survival of DLBCL is poorly understood. However, several recent studies have yielded intriguing findings and shed some light on the possible roles of the microenvironment. In this retrospective study, data from 29 patients diagnosed with DLBCL between 2009 and 2013 were reviewed. All patients had pathologically confirmed DLBCL and had been treated with the R-CHOP regimen. In these patients, we correlated the expression of CD3 staining for T cells, tryptase staining for mast cells, CD68 for tumor-associated macrophages (TAMs), and CD31 staining for blood vessels. CD68 and tryptase expression, as well as MVD, were increased in chemo-resistant patients compared to chemosensitive patients. Tryptase expression showed a positive correlation with MVD, supporting a role for mast cells in DLBCL tumor angiogenesis, while the CD68 correlation with MVD was not significant, indicating a different role for TAMs rather than angiogenesis in DLBCL. A statistically significant difference was observed in the expression of CD3 in patients with bulky disease. Specifically, a higher expression of CD3 was observed in nonbulky disease patients (mean expression 52.91%, n = 20) compared to bulky disease patients (mean expression 34.9%, n = 9), P value < .05. The reduction in T cells in bulky disease patients contributes to loosen the immune control over the tumor, resulting in an increased cell proliferation, leading to large tumor cell masses, which are predictive of poor prognostic and clinical outcomes. CD3 showed a positive correlation with tryptase and MVD, while multiple regression analysis efficaciously predicted MVD depending on CD3 and tryptase as predictors, supporting a complex interplay between these cells in sustaining tumor angiogenesis in DLBCL patients. The improved understanding of tumor biology and of the role of the tumor microenvironment has led to advances in the diagnosis, classification, prognostics, as well as novel treatments of patients with hematologic malignancies. In particular, translational research, leading to drugs that target the interaction between the tumor microenvironment and malignant cells, has provided many promising new approaches to cancer therapy. Ongoing dynamic and correlation studies of tumor biology and the contribution of the tumor microenvironment should be promoted in the context of novel drug development in order to identify optimal therapies for various lymphomas and improve the curability of these diseases.