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C-Reactive Protein Induces Immunosuppression by Activating FcγR2B in Pulmonary Macrophages to Promote Lung Metastasis
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DOI：10.1158/0008-5472.CAN-24-0253.png)
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Abstract
En 中文
C-reactive protein (CRP) is a liver-derived acute phase reactant that is a clinical marker of inflammation associated with poor cancer prognosis. Elevated CRP levels are observed in many types of cancer and are associated with significantly increased risk of metastasis, suggesting that CRP could have prometastatic actions. In this study, we reported that CRP promotes lung metastasis by dampening the anticancer capacity of pulmonary macrophages in breast cancer and melanoma. Deletion of CRP in mice inhibited lung metastasis of breast cancer and melanoma cells without significantly impacting tumor growth compared with wild-type mice. In addition, the lungs of CRP-deficient mice were enriched for activated pulmonary macrophages, which could be reduced to the level of wild-type mice by systemic administration of human CRP. Mechanistically, CRP blocked the activation of pulmonary macrophages induced by commensal bacteria in a Fc gamma R2B-dependent manner, thereby impairing macrophage-mediated immune surveillance to promote the formation of a premetastatic niche in the lungs of tumor-bearing mice. Accordingly, treatment with specific CRP inhibitors activated pulmonary macrophages and attenuated lung metastasis in vivo. These findings highlight the importance of CRP in lung metastasis, which may represent an effective therapeutic target for patients with advanced solid cancers in clinics.Significance: CRP maintains host-commensal tolerance by inhibiting pulmonary macrophage activation and can be targeted to remodel the premetastatic niche in the lung to lower the risk of cancer metastasis.See related commentary by Saal et al., p. 4121
Keywords:
BREAST-CANCER
INHIBITION
ADENOCARCINOMA
LIPOSOMES
THERAPY
CELLS
BINDS
MICE
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