名古屋大学研究人员发现，补体蛋白C3在肿瘤内部局部产生时，可以阻止免疫抑制性髓样细胞进入肿瘤，从而增强抗PD-1抗体免疫疗法的效果[1]。这一发现揭示了一种进化上极为古老的蛋白质——C3在海绵和水母等简单动物中就已存在——在现代癌症治疗中的关键作用[1]。
研究表明，肿瘤组织内局部产生的C3才是真正起效的关键，而循环血液中的C3则不影响治疗效果[1]。实验证实，当肝脏产生的C3减少90%时，抗PD-1抗体免疫疗法仍然有效，但一旦肿瘤内纤维母细胞停止产生C3，同样的治疗效果就会大幅下降，尽管此时循环C3仅下降9%[1]。C3的分解产物iC3b发挥了阻止髓样细胞进入肿瘤的重要作用[1]。
这一机制在肺癌患者样本中得到了验证[1]。数据显示，高局部C3水平的肺癌患者中约50%对治疗有反应，而低水平患者中无人有反应[1]。该研究发表在《自然通讯》杂志[1]。
Researchers at Nagoya University have discovered that the complement protein C3, when produced locally within tumors, can prevent immunosuppressive myeloid cells from infiltrating cancer tissue, thereby enhancing the effectiveness of cancer immunotherapy[1]. The study reveals a critical distinction: C3 circulating in the bloodstream does not influence treatment outcomes, but C3 generated within the tumor microenvironment proves essential[1]. This finding was validated in lung cancer patient samples, where approximately 50 percent of patients with high local C3 levels responded to treatment, compared to zero response among those with low levels[1].
The research demonstrates that C3 is an evolutionarily ancient protein, present in simple organisms such as sponges and jellyfish[1]. When hepatic C3 production was reduced by 90 percent, anti-PD-1 antibody immunotherapy remained effective[1]. However, when tumor fibroblasts ceased producing C3, the same treatment's efficacy declined, with circulating C3 dropping only 9 percent[1]. The mechanism operates through C3 breakdown products, specifically iC3b, which block myeloid cells from entering tumors[1]. The findings were published in Nature Communications in 2026[1].