近日來自上海交通大學(xué)醫(yī)學(xué)院的研究人員在結(jié)腸癌領(lǐng)域取得突破性成果,，在小鼠中CCL20/CCR6軸可作為關(guān)鍵性致病因素推動結(jié)腸癌的發(fā)生發(fā)展,。相關(guān)研究成果發(fā)表在國際著名的《公共科學(xué)圖書館—綜合》（PLoS ONE）雜志上,。
領(lǐng)導(dǎo)這一研究的是上海交大的特聘教授王宏林博士，其2006年獲得德國烏爾姆大學(xué)博士學(xué)位,。
結(jié)腸癌是一種預(yù)后極差的消化系統(tǒng)惡性腫瘤,。近年來，結(jié)腸癌的發(fā)病率逐年上升,，且惡性程度更高,，預(yù)后更差。在這篇文章中,，研究人員證實(shí)腫瘤相關(guān)巨噬細(xì)胞可通過分泌CCL20招募CCR6陽性調(diào)節(jié)性T細(xì)胞,，促進(jìn)小鼠結(jié)腸癌的發(fā)生發(fā)展。課題組以 CCL20 / CCR6軸為控制靶點(diǎn),，通過激活或拮抗趨化因子CCL20受體CCR6的信號傳導(dǎo)通路控制 CCL20 / CCR6系統(tǒng)的功能,。隨后，通過選擇性消除巨噬細(xì)胞的結(jié)腸癌小鼠模型,，研究人員發(fā)現(xiàn),，選擇性消除巨噬細(xì)胞后，結(jié)腸癌小鼠腫瘤微環(huán)境中CCL20的分泌減少,，趨化CCR6陽性調(diào)節(jié)性T細(xì)胞的能力下降,。
該研究成果揭示了在結(jié)腸癌的發(fā)生發(fā)展過程中CCL20/ CCR6軸可作為關(guān)鍵致病因素推動病程進(jìn)展,，對尋找和明確結(jié)腸癌的藥物干預(yù)靶點(diǎn)具有較高學(xué)術(shù)價(jià)值,。（生物谷Bioon.com）
生物谷推薦原文出處：
PLoS ONE DOI:10.1371/journal.pone.0019495
Tumor-Associated Macrophages Recruit CCR6+ Regulatory T Cells and Promote the Development of Colorectal Cancer via Enhancing CCL20 Production in Mice
Jinlin Liu,Ning Zhang,Qun Li,Weiwei Zhang,Fang Ke,Qibin Leng,Hong Wang,Jinfei Chen,Honglin Wang,
Background Tumor-associated macrophages (TAMs) remodel the colorectal cancer (CRC) microenvironment. Yet, findings on the role of TAMs in CRC seem to be contradictory compared with other cancers. FoxP3+ regulatory T (Treg)-cells dominantly infiltrate CRC. However, the underlying molecular mechanism in which TAMs may contribute to the trafficking of Treg-cells to the tumor mass remains unknown. Methodology/Principal Findings CRC was either induced by N-methyl-N-nitrosourea (MNU) and H. pylori or established by subcutaneous injection of mouse colorectal tumor cell line (CMT93) in mice. CMT93 cells were co-cultured with primary macrophages in a transwell apparatus. Recruitment of FoxP3 green fluorescence protein positive (FoxP3GFP+) Treg-cells was assessed using the IVIS Imaging System or immunofluorescence staining. A role for macrophages in trafficking of Treg-cells and in the development of CRC was investigated in CD11b diphtheria toxin receptor (CD11b-DTR) transgenic C57BL/6J mice in which macrophages can be selectively depleted. Treg-cells remarkably infiltrated solid tumor, and predominantly expressed the homing chemokine receptor (CCR) 6 in the induced CRC model. Both CMT93 cancer cells and macrophages produced a large amount of CCL20, the sole ligand of CCR6 in vitro and in vivo. Injection of recombinant mouse CCL20 into tumor sites promoted its development with a marked recruitment of Treg-cells in the graft CRC model. Conditional macrophage ablation decreased CCL20 levels, blocked Treg-cell recruitment and inhibited tumor growth in CD11b-DTR mice grafted with CMT93. Conclusions/Significance TAMs recruit CCR6+ Treg-cells to tumor mass and promote its development via enhancing the production of CCL20 in a CRC mouse model.
