Proinflammatory S100 proteins regulate the accumulation of myeloid-derived suppressor cells.
Proinflammatory S100 proteins regulate the accumulation of myeloid-derived suppressor cells.
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促炎S100蛋白调节髓样衍生的抑制细胞的积累。
DOI：
10.4049/jimmunol.181.7.4666
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发表时间：
2008-10-01
期刊：
影响因子：
--
通讯作者：
Srikrishna G
中科院分区：
文献类型：
--
作者：
Sinha P;Okoro C;Foell D;Freeze HH;Ostrand-Rosenberg S;Srikrishna G
慢性炎症是一个复杂的过程，促进癌变和肿瘤进展;然而，特定的炎症介质促进肿瘤生长的机制仍不清楚。我们和其他人最近证实，炎症介质IL-1β、IL-6和PGE 2可诱导荷瘤个体中髓源性抑制细胞（MDSC）的积聚。MDSC通过抑制T和NK细胞活化，并通过将免疫力极化为促肿瘤2型表型，从而损害肿瘤免疫力，从而促进癌发生和肿瘤进展。我们现在发现，由特定肿瘤诱导的未成熟髓系细胞群体具有共同的表型，无论它们在体内的位置（骨髓、脾脏、血液或肿瘤部位）如何，并且Gr 1highCD 11bhighF 4/80− CD 80 + IL 4 R α+/−精氨酸酶+ MDSC由促炎蛋白S100 A8/A9诱导。S100 A8/A9蛋白与MDSC上晚期糖基化终产物受体和其他细胞表面糖蛋白受体上表达的羧化N-聚糖结合，通过NF-κB途径发出信号，并促进MDSC迁移。MDSC还合成并分泌S100 A8/A9蛋白，其在荷瘤小鼠的血清中积累，并且使用抗羧化聚糖Ab体内阻断S100 A8/A9与MDSC的结合降低了患有转移性疾病的小鼠的血液和次级淋巴器官中的MDSC水平。因此，S100家族的炎症介质作为一个自分泌反馈回路，维持积累的MDSC。由于MDSC的S100 A8/A9活化是通过NF-κB信号传导途径，因此靶向该途径的药物可以降低MDSC水平，并且是与癌症患者的主动免疫疗法结合的有用治疗剂。
Chronic inflammation is a complex process that promotes carcinogenesis and tumor progression; however, the mechanisms by which specific inflammatory mediators contribute to tumor growth remain unclear. We and others recently demonstrated that the inflammatory mediators IL-1β, IL-6, and PGE2 induce accumulation of myeloid-derived suppressor cells (MDSC) in tumor-bearing individuals. MDSC impair tumor immunity and thereby facilitate carcinogenesis and tumor progression by inhibiting T and NK cell activation, and by polarizing immunity toward a tumor-promoting type 2 phenotype. We now show that this population of immature myeloid cells induced by a given tumor share a common phenotype regardless of their in vivo location (bone marrow, spleen, blood, or tumor site), and that Gr1highCD11bhighF4/80−CD80+IL4Rα+/−Arginase+ MDSC are induced by the proinflammatory proteins S100A8/A9. S100A8/A9 proteins bind to carboxylated N-glycans expressed on the receptor for advanced glycation end-products and other cell surface glycoprotein receptors on MDSC, signal through the NF-κB pathway, and promote MDSC migration. MDSC also synthesize and secrete S100A8/A9 proteins that accumulate in the serum of tumor-bearing mice, and in vivo blocking of S100A8/A9 binding to MDSC using an anti-carboxylated glycan Ab reduces MDSC levels in blood and secondary lymphoid organs in mice with metastatic disease. Therefore, the S100 family of inflammatory mediators serves as an autocrine feedback loop that sustains accumulation of MDSC. Since S100A8/A9 activation of MDSC is through the NF-κB signaling pathway, drugs that target this pathway may reduce MDSC levels and be useful therapeutic agents in conjunction with active immunotherapy in cancer patients.
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影响因子：
11.2
作者：
Bunt, Stephanie K.;Yang, Linglin;Ostrand-Rosenberg, Suzanne
通讯作者：
Ostrand-Rosenberg, Suzanne
影响因子：
4.4
作者：
Bronte, V;Serafini, P;Zanovello, P
通讯作者：
Zanovello, P
影响因子：
4.8
作者：
Hunter, MJ;Chazin, WJ
通讯作者：
Chazin, WJ
影响因子：
11.2
作者：
Huang, B;Pan, PY;Chen, SH
通讯作者：
Chen, SH
DOI：
10.1111/j.1365-2222.2011.03714.x
发表时间：
2011-06
期刊：
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
影响因子：
--
作者：
Hofmann Bowman MA;Heydemann A;Gawdzik J;Shilling RA;Camoretti-Mercado B
通讯作者：
Camoretti-Mercado B