Abstract

Lymphomas are characteristic tumors surrounded by an inflammatory microenvironment. The cells of the microenvironment are essential for the growth and survival of neoplastic cells and are recruited through the effect of cytokines/chemokines. Lymphomas include heterogeneous groups of neoplasms infiltrating various lymphoid structures which may arise from B lymphocytes, T lymphocytes, and natural killer (NK) cells at various stages of their differentiation state. In this review article, we analyze the literature data concerning the involvement of the tumor microenvironment (TME) in the progression of lymphomas and the recent advances in the analysis of microenvironment components in the most common forms: some mature B cell lymphoma neoplasms and classic Hodgkin lymphomas. The complex crosstalk between the TME and tumor cells led to the discovery of many mechanisms usable as molecular-targeted therapy through the control of diverse elements of the TME, varying from inhibitors of angiogenic cytokines and their receptors to the regulation of cells’ activities and the novel immune checkpoint inhibitors.

Highlights

  • Follicular lymphoma B-chronic lymphocytic leukemia/small lymphocytic lymphoma Lymphoplasmacytic lymphoma Marginal zone lymphoma T/natural killer large cell granular lymphocyte leukemia T-chronic lymphocytic leukemia/prolymphocytic leukemia

  • B cell-derived lymphomas may originate during any phase of normal B cell differentiation steps, even if most of them are derived from germinal center reactions [4]

  • The indolent lymphomas, whose overall survival is measured in years [8], represent about 40 percent of Non-Hodgkin Lymphomas (NHLs) and include the follicular lymphomas (FL), chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), a fraction of mantle cell lymphomas (MCL) cases, extra-medullary, nodal, and splenic marginal zone lymphomas (MZL), and lymphoplasmacytic lymphomas (LPL)

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Summary

Introduction

Follicular lymphoma B-chronic lymphocytic leukemia/small lymphocytic lymphoma Lymphoplasmacytic lymphoma Marginal zone lymphoma (nodal, extra-nodal, splenic) T/natural killer large cell granular lymphocyte leukemia T-chronic lymphocytic leukemia/prolymphocytic leukemia. DLBCL is characterized by a high heterogeneity at both the clinical and biological levels because it arises from germinal center B cells at different stages of differentiation associated with recurrent genetic modifications which contribute to the molecular pathogenesis of the disease [21]. The higher percentage of tryptase+ mast cells found in the non-responders’ group when compared with the responders’ group positively correlated with the MVD [24], indicating the important role of mast cells in promoting and sustaining tumor angiogenesis in DLBCL.

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