研究發(fā)現(xiàn)缺乏樹(shù)突狀細(xì)胞會(huì)導(dǎo)致胰腺癌患者免疫功能異常
2020-03-18
來(lái)源：小柯機(jī)器人
華盛頓大學(xué)醫(yī)學(xué)院David G. DeNardo研究小組取得一項(xiàng)新突破。他們的研究發(fā)現(xiàn)缺乏樹(shù)突狀細(xì)胞會(huì)導(dǎo)致胰腺癌患者免疫功能異常。2020年3月16日，《癌細(xì)胞》發(fā)表了這一成果。
研究人員利用胰腺和肺癌的自發(fā)模型來(lái)檢測(cè)新生抗原如何重塑腫瘤免疫及其進(jìn)展。正如研究人員的猜想，在肺腺癌發(fā)生過(guò)程中新生抗原會(huì)誘導(dǎo)T細(xì)胞介導(dǎo)的免疫和疾病抑制。相比之下，胰腺導(dǎo)管腺癌（PDAC）中的新生抗原會(huì)導(dǎo)致促進(jìn)疾病發(fā)展和轉(zhuǎn)移的炎性纖維微環(huán)境惡化。
致病性TH17應(yīng)答是PDAC中新生抗原促進(jìn)腫瘤進(jìn)展的原因。這些T細(xì)胞在胰腺和肺癌中應(yīng)答不同的原因是由浸潤(rùn)性保守樹(shù)突狀細(xì)胞（cDC）的差異造成。
在早期PDAC中克服cDC缺乏可抑制疾病進(jìn)展，而在進(jìn)展期PDAC中恢復(fù)cDC功能可挽救抑制腫瘤的免疫并增強(qiáng)對(duì)放射治療的反應(yīng)性。
附：英文原文
Title: Dendritic Cell Paucity Leads to Dysfunctional Immune Surveillance in Pancreatic Cancer
Author: Samarth Hegde, Varintra E. Krisnawan, Brett H. Herzog, Chong Zuo, Marcus A. Breden, Brett L. Knolhoff, Graham D. Hogg, Jack P. Tang, John M. Baer, Cedric Mpoy, Kyung Bae Lee, Katherine A. Alexander, Buck E. Rogers, Kenneth M. Murphy, William G. Hawkins, Ryan C. Fields, Carl J. DeSelm, Julie K. Schwarz, David G. DeNardo
Issue&Volume: 2020/03/16
Abstract: Here, we utilized spontaneous models of pancreatic and lung cancer to examine how neoantigenicity shapes tumor immunity and progression. As expected, neoantigen expression during lung adenocarcinoma development leads to T cell-mediated immunity and disease restraint. By contrast, neoantigen expression in pancreatic ductal adenocarcinoma (PDAC) results in exacerbation of a fibro-inflammatory microenvironment that drives disease progression and metastasis. Pathogenic TH17 responses are responsible for this neoantigen-induced tumor progression in PDAC. Underlying these divergent T cell responses in pancreas and lung cancer are differences in infiltrating conventional dendritic cells (cDCs). Overcoming cDC deficiency in early-stage PDAC leads to disease restraint, while restoration of cDC function in advanced PDAC restores tumor-restraining immunity and enhances responsiveness to radiation therapy.
DOI: 10.1016/j.ccell.2020.02.008
Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30097-0
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