Tuft and Cancer Stem Cell Marker DCLK1: A New Target to Enhance Anti-Tumor Immunity in the Tumor Microenvironment.
Tuft and Cancer Stem Cell Marker DCLK1: A New Target to Enhance Anti-Tumor Immunity in the Tumor Microenvironment.
复制标题
DOI：
10.3390/cancers12123801
复制
发表时间：
2020-12-17
期刊：
影响因子：
5.2
通讯作者：
Qu D
中科院分区：
文献类型：
--
作者：
Cao Z;Weygant N;Chandrakesan P;Houchen CW;Peng J;Qu D
双皮质素样激酶1（DCLK 1）是结肠癌、胰腺癌和其他潜在癌症的肿瘤干细胞标志物，近年来受到广泛关注。除了其作为正常组织中的簇细胞标记物和作为癌症中的肿瘤干细胞标记物的作用外，先前的研究已经证明沉默DCLK 1在功能上减少癌症中的干细胞、上皮间质转化（EMT）和肿瘤发生。最近，DCLK 1在调节炎症、癌前病变和肿瘤微环境中的作用，包括其调节免疫细胞机制的能力，已开始受到关注。重要的是，靶向DCLK 1的临床上可行的治疗手段最终以激酶抑制剂、单克隆抗体和嵌合抗原受体T细胞（CAR-T）的形式变得可用。本文综述了DCLK 1在肿瘤微环境中的作用机制，并评估了DCLK 1在结肠癌、胰腺癌和肾癌中的靶向作用。微管相关的双皮质素样激酶1（DCLK 1）是公认的簇细胞（TC）和多种癌症干细胞（CSC）的标志物，并且新的证据表明DCLK 1阳性TC参与炎症相关癌症的起始和形成。表达DCLK 1的CSC调节癌症中的多种生物学过程，促进对治疗的抗性，并与转移相关。在实体瘤癌症中，肿瘤上皮细胞、免疫细胞、癌症相关成纤维细胞、内皮细胞和血管、细胞外基质和缺氧都支持以耐药性、复发和转移为特征的CSC表型。最近的研究表明，DCLK 1阳性的CSC与上皮-间质转化、血管生成和免疫检查点有关。关于用小分子抑制剂、单克隆抗体和嵌合抗原受体T细胞靶向DCLK 1的新数据显示出抑制肿瘤生长和调节肿瘤免疫微环境的有希望的效果。总的来说，DCLK 1作为抗癌靶点正在成熟，针对它的治疗可能具有直接对抗CSC的潜力，重塑肿瘤微环境，并作为免疫疗法。
Doublecortin-like kinase 1 (DCLK1) is a tumor stem cell marker in colon, pancreatic, and potentially other cancers that has received wide attention recently. Aside from its role as a tuft cell marker in normal tissue and as a tumor stem cell marker in cancer, previous studies have demonstrated that silencing DCLK1 functionally reduces stemness, epithelial mesenchymal transition (EMT), and tumorigenesis in cancers. More recently, DCLK1′s role in regulating the inflammatory, pre-cancer, and tumor microenvironment including its ability to modulate immune cell mechanisms has started to come into focus. Importantly, clinically viable therapeutic means of targeting DCLK1 have finally become available in the form of kinase inhibitors, monoclonal antibodies, and chimeric antigen receptor T cells (CAR-T). Herein, we comprehensively review the mechanistic role of DCLK1 in the tumor microenvironment, assess the potential for targeting DCLK1 in colon, pancreatic and renal cancer. Microtubule-associated doublecortin-like kinase 1 (DCLK1) is an accepted marker of tuft cells (TCs) and several kinds of cancer stem cells (CSCs), and emerging evidence suggests that DCLK1-positive TCs participate in the initiation and formation of inflammation-associated cancer. DCLK1-expressing CSCs regulate multiple biological processes in cancer, promote resistance to therapy, and are associated with metastasis. In solid tumor cancers, tumor epithelia, immune cells, cancer-associated fibroblasts, endothelial cells and blood vessels, extracellular matrix, and hypoxia all support a CSC phenotype characterized by drug resistance, recurrence, and metastasis. Recently, studies have shown that DCLK1-positive CSCs are associated with epithelial-mesenchymal transition, angiogenesis, and immune checkpoint. Emerging data concerning targeting DCLK1 with small molecular inhibitors, monoclonal antibodies, and chimeric antigen receptor T-cells shows promising effects on inhibiting tumor growth and regulating the tumor immune microenvironment. Overall, DCLK1 is reaching maturity as an anti-cancer target and therapies directed against it may have potential against CSCs directly, in remodeling the tumor microenvironment, and as immunotherapies.
登录
查看更多内容
影响因子：
64.8
作者：
Gerbe F;Sidot E;Smyth DJ;Ohmoto M;Matsumoto I;Dardalhon V;Cesses P;Garnier L;Pouzolles M;Brulin B;Bruschi M;Harcus Y;Zimmermann VS;Taylor N;Maizels RM;Jay P
通讯作者：
Jay P
影响因子：
29.4
作者：
Dandawate, Prasad;Ghosh, Chandrayee;Dhar, Animesh
通讯作者：
Dhar, Animesh
影响因子：
2.3
作者：
Hass, Nicole;Schwarzenbacher, Karin;Breer, Heinz
通讯作者：
Breer, Heinz
影响因子：
82.9
作者：
Binnewies M;Roberts EW;Kersten K;Chan V;Fearon DF;Merad M;Coussens LM;Gabrilovich DI;Ostrand-Rosenberg S;Hedrick CC;Vonderheide RH;Pittet MJ;Jain RK;Zou W;Howcroft TK;Woodhouse EC;Weinberg RA;Krummel MF
通讯作者：
Krummel MF
影响因子：
64.8
作者：
Fischer KR;Durrans A;Lee S;Sheng J;Li F;Wong ST;Choi H;El Rayes T;Ryu S;Troeger J;Schwabe RF;Vahdat LT;Altorki NK;Mittal V;Gao D
通讯作者：
Gao D