Abstract
Complement, as a central immune surveillance system, can be activated within seconds upon stimulation, thereby displaying multiple immune effector functions. However, in pathologic scenarios (like in tumor progression), activated complement can both display protective effects to control tumor development and passively promotes the tumor growth. Clinical investigations show that patients with several hematological malignancies often display abnormal level of specific complement components, which in turn modulates complement activation or deregulated cascade. In the past decades, complement-dependent cytotoxicity and complement-dependent cell-mediated phagocytosis were fully approved to display vital roles in monoclonal antibody-based immunotherapies, especially in therapies against hematological malignancies. However, tumor-mediated complement evasion presents a big challenge for such a therapy. This review aims to provide an integrative overview on the roles of the complement in tumor promotion, highlights complement mediated effects on antibody-based immunotherapy against distinct hematological tumors, hopefully provides a theoretical basis for the development of complement-based cancer targeted therapies.
Highlights
Complement was initially identified more than 100 years ago due to a result of its bactericidal activity ‘complementary’ to the action of immunoglobulins and the role in phagocytosis of cellular debris [1, 2]
As an essential part of innate immunity and an evolutionary old system, complement is highly conserved among a wide variety of species, emphasizing its importance in immune defense throughout evolution [3]
Clinical investigations show that patients with hematological malignancies often display abnormal level of complement components, which in turn modulates complement activation
Summary
Complement was initially identified more than 100 years ago due to a result of its bactericidal activity ‘complementary’ to the action of immunoglobulins and the role in phagocytosis of cellular debris [1, 2]. Complement-dependent cytotoxicity (CDC) and complement-dependent cell-mediated phagocytosis (CDCP) were fully approved to display vital roles in maintaining homeostasis, fighting against infection and even in monoclonal antibody-based immunotherapies, Hematological Malignancies and Complement especially in therapies against hematological malignancies. Clinical investigations show that patients with hematological malignancies often display abnormal level of complement components, which in turn modulates complement activation. Over the past two decades, significant progress has been made for the development of monoclonal antibody (mAb) therapies for hematologic malignancies. AntiCD20 mAbs, mainly rituximab (RTX) or obinutuzumab, combined with chemotherapy agents have been approved for treatment of diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL), respectively [7, 8]. Complement-dependent cytotoxicity and complement-dependent cell-mediated phagocytosis display vital roles in mAb-based immunotherapies. Tumormediated complement evasion might be a big challenge for such a therapy
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