Intraperitoneal neutrophils activated by KRAS-induced ovarian cancer exert antitumor effects by modulating adaptive immunity.
Intraperitoneal neutrophils activated by KRAS-induced ovarian cancer exert antitumor effects by modulating adaptive immunity.
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DOI：
10.3892/ijo.2018.4504
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发表时间：
2018-10
影响因子：
5.2
通讯作者：
Fujii T
中科院分区：
文献类型：
--
作者：
Yoshida M;Taguchi A;Kawana K;Ogishima J;Adachi K;Kawata A;Nakamura H;Sato M;Fujimoto A;Inoue T;Tomio K;Mori M;Nagamatsu T;Arimoto T;Koga K;Hiraike OW;Oda K;Kiyono T;Osuga Y;Fujii T
中性粒细胞计数增加是癌症预后不良的标志。我们之前曾报道，KRAS促进了小鼠腹膜癌模型的肿瘤形成并增加了中性粒细胞计数。在目前的研究中，我们评估了中性粒细胞增加在癌症进展中的作用，以及它们对腹膜微环境的影响。用转导KRAS基因的小鼠卵巢癌细胞株ID8-KRAS建立小鼠腹膜癌模型。用中性粒细胞耗竭的方法评估ID8-KRAS小鼠的中性粒细胞功能。中性粒细胞的减少明显加速了肿瘤的形成；这伴随着腹水中白细胞介素6浓度的增加。去中性粒细胞后，局部和全身CD8+T细胞数量显著减少，而局部CD4+T细胞数量增加，同时单核细胞髓系来源抑制细胞(M-MDSCs)和调节性T细胞(Tregs)数量增加(P<；0.05)。体外检测腹膜中性粒细胞(PEN)在CD8+T细胞活化中的作用。与外周血中性粒细胞(PBN)相比，ID8-KRAS小鼠的PENS具有很强的促进T细胞增殖的能力，其T细胞共刺激分子OX40L和4-1BB配体(4-1BBL)的表达水平高于外周血中性粒细胞(PBN)。这些发现表明，在KRAS诱导的肿瘤微环境(TME)中招募的中性粒细胞具有抗肿瘤特性，可能通过T细胞共刺激分子调节M-MDSCs和Tregs的数量，并激活CD8+T细胞。
Increased neutrophil counts are a hallmark of a poor prognosis for cancer. We previously reported that KRAS promoted tumorigenesis and increased neutrophil counts in a mouse peritoneal cancer model. In the current study, we evaluated the role of increased neutrophils in cancer progression, as well as their influence on the intraperitoneal microenvironment. A mouse peritoneal cancer model was established using the KRAS-transduced mouse ovarian cancer cell line, ID8-KRAS. Neutrophil function was assessed by neutrophil depletion in ID8-KRAS mice. Neutrophil depletion markedly accelerated tumor formation; this was accompanied by an increase in interleukin-6 concentrations in ascites. Neutrophil depletion significantly decreased the amount of local and systemic CD8+ T cells, while increasing the amount of local CD4+ T cells, accompanied by an increased amount of monocytic myeloid-derived suppressor cells (M-MDSCs) and regulatory T cells (Tregs) (P<0.05). The roles of peritoneal neutrophils (PENs) in CD8+ T cell activation were assessed in vitro. PENs of ID8-KRAS mice had a strong potential to enhance T cell proliferation with a higher expression of the T cell costimulatory molecules OX40 ligand (OX40L) and 4-1BB ligand (4-1BBL), as compared with peripheral blood neutrophils (PBNs). These findings suggest that neutrophils recruited into the KRAS-induced tumor microenvironment (TME) have antitumor properties with the potential to modulate the numbers of M-MDSCs and Tregs and activate CD8+ T cells through T cell costimulatory molecules.
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结直肠癌瘤内中性粒细胞增多与恶性表型密切相关，可预测患者的不良预后。
影响因子：
3.7
作者：
Rao HL;Chen JW;Li M;Xiao YB;Fu J;Zeng YX;Cai MY;Xie D
通讯作者：
Xie D
影响因子：
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Antonarakis ES
影响因子：
8.8
作者：
Eser, S.;Schnieke, A.;Schneider, G.;Saur, D.
通讯作者：
Saur, D.
影响因子：
8.8
作者：
Scambia, G.;Testa, U.;Benedetti Panici, P.;Foti, E.;Martucci, R.;Gadducci, A.;Perillo, A.;Facchini, V.;Peschle, C.;Mancuso, S.
通讯作者：
Mancuso, S.