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The Role of Complement in Tumors

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Front. Immunol. | doi: 10.3389/fimmu.2018.02203

Complement as a biological tool to control tumor growth

 Paolo Macor1, Sara Capolla1 and  Francesco Tedesco2*
  • 1Department of Life Sciences, University of Trieste, Italy
  • 2Department of Life Sciences, Istituto Auxologico Italiano (IRCCS), Italy

Deposits of complement components have been documented in several human tumors suggesting a potential involvement of the complement system in tumor immune surveillance. In vitro and in vivo studies have revealed a double role played by this system in tumor progression. Complement activation in the cancer microenvironment has been shown to promote cancer growth through the release of the chemotactic peptide C5a recruiting myeloid suppressor cells. There is also evidence that tumor progression can be controlled by complement activated on the surface of cancer cells through one of the three pathways of complement activation. The aim of this review is to discuss the protective role of complement in cancer with special focus on the beneficial effect of complement-fixing antibodies that are efficient activators of the classical pathway and contribute to inhibit tumor expansion as a result of MAC-mediated cancer cell killing and complement-mediated inflammatory process. Cancer cells are heterogeneous in their susceptibility to complement-induced killing that generally depends on stable and relatively high expression of the antigen and the ability of therapeutic antibodies to activate complement. A new generation of monoclonal antibodies is​ being developed with structural modification leading to hexamer formation and enhanced complement activation. An important progress in cancer immunotherapy has been made with the generation of bispecific antibodies targeting tumor antigens and able to neutralize complement regulators overexpressed on cancer cells. A great effort is being devoted to implementing combined therapy of traditional approaches based on surgery, chemotherapy and radiotherapy and complement-fixing therapeutic antibodies. An effective control of tumor growth by complement is likely to be obtained on residual cancer cells following conventional therapy to reduce the tumor mass, prevent recurrences and avoid disabilities.

Keywords: Complement system activation, Tumor control, Antibody-based immunotherapy, Combination therapies, Antibody development

Received: 29 Jun 2018; Accepted: 05 Sep 2018.

Edited by:

Maciej M. Markiewski, Texas Tech University Health Sciences Center, United States

Reviewed by:

Fabian Benencia, Ohio University, United States
Ronald P. Taylor, University of Virginia, United States  

Copyright: © 2018 Macor, Capolla and Tedesco. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Francesco Tedesco, Istituto Auxologico Italiano (IRCCS), Department of Life Sciences, Milan, 34127, Italy, tedesco@units.it