Understanding the role of C5a/C5aR1-mediated complement activation pathway in tumor progression and therapy resistance

The complement system is crucial to the malignant progression of tumors. However, most previous studies have focused on the immune-related roles of complement pathways, with limited attention to their direct effects on tumor cells. Recent research highlights the involvement of complement pathways in immune regulation of normal cells, adaptive immune response shaping, tumor growth, metastasis, angiogenesis, tumor microenvironment remodeling, and regulation of immune tolerance. In this review, we summarize the tissue distribution and expression regulation of the complement key molecule C5a and its receptor C5aR1 in tumors, their roles and mechanisms in tumor malignant progression and the development of therapeutic resistance, as well as the clinical value of C5a/C5aR1 in diagnosis and treatment. These findings may identify a novel therapeutic target, offering new strategies for the diagnosis and treatment of tumors.