Disease-induced immunomodulation at biomaterial scaffolds detects early pancreatic cancer in a spontaneous model.
Disease-induced immunomodulation at biomaterial scaffolds detects early pancreatic cancer in a spontaneous model.
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疾病诱导的免疫调节在生物材料支架检测早期胰腺癌的自发模型。
DOI：
10.1016/j.biomaterials.2020.120632
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发表时间：
2021-03
期刊：
影响因子：
14
通讯作者：
Shea LD
中科院分区：
文献类型：
--
作者：
Bushnell GG;Orbach SM;Ma JA;Crawford HC;Wicha MS;Jeruss JS;Shea LD
由于疾病侵袭性和缺乏早期检测平台，胰腺癌是所有癌症中预后最差的。我们开发了生物材料支架，招募转移性肿瘤细胞并反映天然转移部位的免疫失调。虽然该平台在原位乳腺癌模型中显示出前景，但其在其他模型中的潜力尚未得到检验。在此，我们证明了在腺癌形成之前，在自发性胰腺癌的KPCY模型中，支架招募了弥散性胰腺细胞（支架YFP+细胞增加了3倍）。此外，支架上的免疫细胞区分早期和晚期疾病的准确性（0.83）高于自然转移部位（肝脏，0.50）。通过单核细胞增加约2倍来确定早期疾病。晚期疾病的特征是T细胞和自然杀伤细胞增加1.5 - 2倍。差异免疫反应表明该支架可以区分自发性胰腺癌和自发性乳腺癌。总的来说，我们的研究结果证明了支架在两种自发肿瘤发生模型中反映免疫调节的效用，以及它们在侵袭性KPCY胰腺癌模型中识别早期疾病阶段的特殊效用。这种支架可以作为早期发现胰腺癌的平台，以改善治疗和预后。
Pancreatic cancer has the worst prognosis of all cancers due to disease aggressiveness and paucity of early detection platforms. We developed biomaterial scaffolds that recruit metastatic tumor cells and reflect the immune dysregulation of native metastatic sites. While this platform has shown promise in orthotopic breast cancer models, its potential in other models is untested. Herein, we demonstrate that scaffolds recruit disseminated pancreatic cells in the KPCY model of spontaneous pancreatic cancer prior to adenocarcinoma formation (3-fold increase in scaffold YFP+ cells). Furthermore, immune cells at the scaffolds differentiate early and late stage disease with greater accuracy (0.83) than the natural metastatic site (liver, 0.50). Early disease was identified by an approximately 2-fold increase in monocytes. Late stage disease was marked by a 1.5–2-fold increase in T cells and natural killer cells. The differential immune response indicated that the scaffolds could distinguish spontaneous pancreatic cancer from spontaneous breast cancer. Collectively, our findings demonstrate the utility of scaffolds to reflect immunomodulation in two spontaneous models of tumorigenesis, and their particular utility for identifying early disease stages in the aggressive KPCY pancreatic cancer model. Such scaffolds may serve as a platform for early detection of pancreatic cancer to improve treatment and prognosis.
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影响因子：
11.8
作者：
Feinberg TY;Zheng H;Liu R;Wicha MS;Yu SM;Weiss SJ
通讯作者：
Weiss SJ
影响因子：
--
作者：
Lee JW;Komar CA;Bengsch F;Graham K;Beatty GL
通讯作者：
Beatty GL
影响因子：
78.5
作者：
Klein, Christoph A.
通讯作者：
Klein, Christoph A.
DOI：
10.1084/jem.20101876
发表时间：
2011-03-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
De Monte L;Reni M;Tassi E;Clavenna D;Papa I;Recalde H;Braga M;Di Carlo V;Doglioni C;Protti MP
通讯作者：
Protti MP
DOI：
10.1073/pnas.1208384109
发表时间：
2012-11-27
影响因子：
11.1
作者：
Lee, Jungwoo;Li, Matthew;Parekkadan, Biju
通讯作者：
Parekkadan, Biju