The challenge of the microenvironment in B-cell lymphomas

Abstract

B-cell non-Hodgkin lymphomas (B-NHL) represent the most common malignant lymphoid neoplasms, with the majority of these arising from germinal centre or post-germinal centre B cells, due to (at least) a disruption of the different phases of normal B-cell development. The most common B-cell lymphoma subtypes include follicular lymphoma, diffuse large B-cell lymphoma, marginal zone lymphoma and mantle cell lymphoma. As with other malignancies, it has been demonstrated that the development and progression of B-cell lymphomas involves complex interactions between the neoplastic B-cells and the surrounding microenvironment, including stromal cells, the intratumoral vasculature, the various types of macrophages, as well as T-cells, including regulatory T-cells (also termed T-regs). The complex communications between the cell populations involves interplay between chemokines, chemokine receptors and adhesion molecules, and the balance between these determines whether there is a tumour cell growth promotion or inhibition. The demonstration of the importance of the microenvironment in B-NHL has been shown recently using methodologies such as gene expression profiling, and has been validated in some B-NHL lymphoma subtypes using other techniques, such as immunohistochemistry. This is particularly in the case of follicular lymphomas, in which both T-regs and macrophages have been demonstrated to have prognostic value. As such, the microenvironment of B-cell lymphomas represents a challenge to the development of therapeutic agents, requiring re-direction and inclusion of these non-neoplastic supportive cells into future treatment strategies.

LNA-mediated anti–miR-155 silencing in low-grade B-cell lymphomas

“…[45][46][47] In the present study, we found higher miR-155 levels in the stromal cells of patients with WM compared with those from healthy subjects ( Figure 4A). Interestingly, loss of miR-155 in the stroma led to significant inhibition of tumor growth, indicating that miR-155 regulates tumor proliferation not only when it is overexpressed in the malignant cells, but also when it is present in BM microenvironmental cells (Figure 4).…”

Intratumoral heterogeneity of F-18 FDG uptake differentiates between gastrointestinal stromal tumors and abdominal malignant lymphomas on PET/CT

“…MLs are malignant neoplasms composed of monoclonal proliferations of lymphocytes derived from either B cells or T cells at various stages of their differentiation [10]. The molecular characteristics and biologic behavior of these tumors differ according to the histologic subtype.…”

In Vitro Modeling of Tissue-Specific 3D Microenvironments and Possibile Application to Pediatric Cancer Research

“…The resulting tumor growth depends on the balance between the inhibitory and growth-promoting signals [176,177]. Thus, in each tissue, lymphoma cells presents an unique network of signals, and therefore is hard to get targeted therapies [175,178].…”