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Abstract
Colorectal cancer (CRC) is the third most common malignant tumor and the second most fatal cancer worldwide. Several parts of the immune system contribute to fighting cancer including the innate complement system. The complement system is composed of several players, namely component molecules, regulators and receptors. In this review, we discuss the complement system activation in cancer specifically CRC and highlight the possible interactions between the complement system and the various TME components. Additionally, the role of the complement system in tumor immunity of CRC is reviewed. Hence, such work could provide a framework for researchers to further understand the role of the complement system in CRC and explore the potential therapies targeting complement activation in solid tumors such as CRC.
Highlights
TO COLORECTAL CANCERColorectal cancer (CRC) is the third most common malignant tumor and the second most fatal cancer in the world
T cells recognize self from non-self by the binding of T cell receptors (TCR) to major histocompatibility I (MHC I) that is expressed on the surface of tumor cells [9, 10]
After showing an initial success in the treatment of melanoma, immunotherapy has been evolving as a promising strategy for many solid tumors including CRC [12]
Summary
The complement system is one of the first lines of defence against foreign pathogens or stressed cells, as a major part of our innate immune system. In CRC, tumor cells were found to produce C3 component leading to modulation of the response of macrophages and its anti-tumor immunity, via the C3a-C3aR axis and PI3Kg signaling pathways [90]. In CRC, the C5a component was generated by serine proteases on the surface of tumor cells independent of complement activation [100], while the C5a/C5aR pathway was found to induce cell proliferation, motility, and invasiveness [101, 102]. Blocking of this pathway was demonstrated to improve the response to PD-L1 therapy in CRC [103]. Under investigation in kidney transplant patients Acute respiratory distress syndrome due to COVID-19 (SAVE trial) Periodontal inflammation Paroxysmal nocturnal hemoglobinuria Geographic atrophy Paroxysmal nocturnal hemoglobinuria Acute hemolytic uremic syndrome Myasthenia gravis Neuromyelitis optica Severe COVID-19 Preclinical in mice Suggestive for neurodegenerative diseases Bullous Pemphigoid Advanced solid tumors Multiple myeloma Cervical cancer Cervical cancer
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