Abstract
Emerging evidence reveals a significant shift in understanding the complement system's role in cancer, where activation of a complement within the tumor microenvironment (TME) fuels tumor growth and metastasis instead of suppressing it. Research highlights C3a and C5a anaphylatoxins as key drivers of cancer progression, showing that the blockade of their signaling pathways can inhibit tumor growth and metastasis. By interacting with immune cells in the TME, including tumor-associated macrophages (TAMs), T cells, and myeloid-derived suppressor cells, C3a and C5a promote immunosuppression, thereby driving cancer cell proliferation, angiogenesis, and metastasis. However, conflicting findings persist, despite growing evidence supporting the role of C3a and C5a in tumor progression and the potential therapeutic benefits of targeting pathological complement activation. This paper presents a systematic review of studies examining the activation of the complement system and the role of the C3a and C5a signaling pathways in the TME, focusing on their effects on tumor progression, their interactions with TME components, and the potential for targeting these signaling pathways to boost anti-tumor immune responses.