Tumor Microenvironment in Diffuse Large B-Cell Lymphoma:Role and Prognosis

Diffuse large B-cell lymphoma (DLBCL) represents 30-40% of all non-Hodgkin lymphomas (NHL) and is a disease with an aggressivebehavior. Because about one-third of DLBCL patients will be refractory or resistant to standard therapy, several studies focused onidentification of new individual prognostic and risk stratification biomarkers and new potential therapeutic targets. In contrast toother types of cancers like carcinomas, where tumor microenvironment was widely investigated, its role in DLBCL pathogenesisand patient survival is still poorly understood, although few studies had promising results. The composition of TME and itsinteraction with neoplastic cells may explain the role of several genes (beta2-microglobulin gene, CD58 gene), receptor-likeprogrammed cell death-1 (PD-1) and its ligand (PD-L1), or other cell components (Treg) in tumor evasion of immunesurveillance, resulting in tumor progression. Also, it was found that“gene expression profile”of the microenvironmental cells, thephenotype of tumor-associated macrophages (TAM), the expression of matricellular proteins like SPARC andfibronectin, theoverexpression of several types of matrix metalloproteinases (MMPs) like MMP-2 and MMP-9, or the tissue inhibitors of matrixmetalloproteinases (TIMPs) may lead to a favorable or adverse outcome. With this review, we try to highlight the influence ofmicroenvironment components over lymphoid clone progression and their prognostic impact in DLBCL patients