B-cell non-Hodgkin lymphoma: importance of angiogenesis and antiangiogenic therapy
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REVIEW PAPER
B-cell non-Hodgkin lymphoma: importance of angiogenesis and antiangiogenic therapy Lei Jiang1,2 · Nailin Li2 Received: 9 February 2020 / Accepted: 11 May 2020 © Springer Nature B.V. 2020
Abstract Angiogenesis is critical for the initiation and progression of solid tumors, as well as hematological malignancies. While angiogenesis in solid tumors has been well characterized, a large body of investigation is devoted to clarify the impact of angiogenesis on lymphoma development. B-cell non-Hodgkin lymphoma (B-NHL) is the most common lymphoid malignancy with a highly heterogeneity. The malignancy remains incurable despite that the addition of rituximab to conventional chemotherapies provides substantial improvements. Several angiogenesis-related parameters, such as proangiogenic factors, circulating endothelial cells, microvessel density, and tumor microenvironment, have been identified as prognostic indicators in different types of B-NHL. A better understanding of how these factors work together to facilitate lymphoma-specific angiogenesis will help to design better antiangiogenic strategies. So far, VEGF-A monoclonal antibodies, receptor tyrosine kinase inhibitors targeting VEGF receptors, and immunomodulatory drugs with antiangiogenic activities are being tested in preclinical and clinical studies. This review summarizes recent advances in the understanding of the role of angiogenesis in B-NHL, and discusses the applications of antiangiogenic therapies. Keywords B-cell lymphoma · VEGF · Angiogenesis · Antiangiogenic therapy
Introduction Lymphomas are a diverse group of neoplastic disorders that arise from lymphocytes at various stages of development. They are classified into Hodgkin’s lymphoma (HL) and non-Hodgkin lymphoma (NHL). The latter represents about 90% of all lymphomas, with various indolent and aggressive malignancies. Of these, over 80% are originated from B-cells (B-NHL), whereas the remaining lymphomas are originated from T cells or NK cells. The World Health Organization (WHO) classification lists over 40 mature B-cell neoplasms and the current review focuses on the most common subtypes of B-NHL including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma * Lei Jiang [email protected] 1
Department of Pathology, Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China
Department of Medicine‑Solna, Clinical Pharmacology Group, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden
2
(MCL), Burkitt lymphoma (BL), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Angiogenesis, the formation of new blood vessels from pre-existing vascular network, is distinct from vasculogenesis, which depicts the process of neovascularization by de novo-generated endothelial cells or circulating bone marrowderived endothelial progenitor cells (EPCs) during development. Angiogenesis generally occurs in two forms. The first is the sprouting angiogenesis, which is ind
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