The contribution of the CRP/CD64 axis to renal cancer progression by inducing protumor activation of tumor-associated macrophages

被引:1
作者
Pan, Cheng [1 ]
Fujiwara, Yukio [1 ]
Yano, Hiromu [1 ]
Anami, Toshiki [1 ,2 ]
Ibe, Yuki [1 ,2 ]
Li, Lianbo [1 ,3 ]
Miura, Yuji [1 ,4 ]
Motoshima, Takanobu [2 ]
Esumi, Shigeyuki [5 ]
Yatsuda, Junji [2 ]
Hibi, Taizo [3 ]
Kamba, Tomomi [2 ]
Komohara, Yoshihiro [1 ,6 ]
机构
[1] Kumamoto Univ, Grad Sch Med Sci, Dept Cell Pathol, Honjo 1-1-1, Kumamoto 8608556, Japan
[2] Kumamoto Univ, Grad Sch Med Sci, Dept Urol, Kumamoto, Japan
[3] Kumamoto Univ, Grad Sch Med Sci, Dept Pediat Surg & Transplantat, Kumamoto, Japan
[4] Toranomon Gen Hosp, Dept Med Oncol, Tokyo, Japan
[5] Kumamoto Univ, Grad Sch Med Sci, Dept Anat & Neurobiol, Kumamoto, Japan
[6] Kumamoto Univ, Ctr Metab Regulat Hlth Aging, Kumamoto, Japan
基金
日本学术振兴会;
关键词
CD64; CRP; IL6; macrophage; PD-L1; renal cell carcinoma; C-REACTIVE PROTEIN; FC-GAMMA-RI; RECEPTOR; EXPRESSION; PD-L1; PHASE;
D O I
10.1002/cti2.70013
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
ObjectivesC-reactive protein (CRP) is a well-known acute-phase protein that increases remarkably under various inflammatory conditions and is elevated in patients with malignant tumors. In this study, we investigated the influence of CRP on the tumor microenvironment in clear cell renal cell carcinoma (ccRCC).MethodsThis study explored CRP's role in ccRCC by co-culturing human macrophages with ccRCC cells and employing antibody blocking, RNA sequencing and in vitro experiments for functional insights. We also analysed The Cancer Genome Atlas Program (TCGA) data to link CD64 expression with ccRCC prognosis and used immunohistochemistry to associate CD64+ macrophages with tumor severity and systemic CRP levels.ResultsA co-culture study using human macrophages and RCC cell lines showed that CRP-stimulated macrophages secrete IL-6, which induces RCC proliferation via STAT3 activation. CRP-induced protumor activation of macrophages was suppressed by CD64 blocking antibodies. Furthermore, CRP elevates PD-L1 expression in macrophages via the CD64-STAT1 signalling pathway. Statistical analysis of TCGA data indicated that increased CD64 expression was associated with a worse clinical course in ccRCC. Immunohistochemical analysis of pathological specimens revealed that high CD64 expression in tumor-associated macrophages (TAMs), and a high density of CD64+ TAMs, was linked to high nuclear grade and stage. High CD64 expression was also correlated with increased serum CRP levels.ConclusionsThe CRP-CD64 signal was linked to the protumor activation of TAMs and could be a promising target for anticancer immunotherapy in ccRCC.
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页数:14
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