华盛顿大学医学院David G. DeNardo研究小组取得一项新突破。他们的研究发现缺乏树突状细胞会导致胰腺癌患者免疫功能异常。2020年3月16日，《癌细胞》发表了这一成果。

研究人员利用胰腺和肺癌的自发模型来检测新生抗原如何重塑肿瘤免疫及其进展。正如研究人员的猜想，在肺腺癌发生过程中新生抗原会诱导T细胞介导的免疫和疾病抑制。相比之下，胰腺导管腺癌（PDAC）中的新生抗原会导致促进疾病发展和转移的炎性纤维微环境恶化。

致病性T_H17应答是PDAC中新生抗原促进肿瘤进展的原因。这些T细胞在胰腺和肺癌中应答不同的原因是由浸润性保守树突状细胞（cDC）的差异造成。

在早期PDAC中克服cDC缺乏可抑制疾病进展，而在进展期PDAC中恢复cDC功能可挽救抑制肿瘤的免疫并增强对放射治疗的反应性。

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