胰腺癌
免疫系统
癌症研究
免疫
免疫学
癌症
医学
生物
内科学
作者
Joshua Leinwand,George Miller
出处
期刊:Nature Immunology
[Springer Nature]
日期:2020-08-17
卷期号:21 (10): 1152-1159
被引量:114
标识
DOI:10.1038/s41590-020-0761-y
摘要
Pancreatic ductal adenocarcinoma carries a dismal prognosis, and outcomes have improved little with modern therapeutics. Checkpoint-based immunotherapy has failed to elicit responses in the vast majority of patients with pancreatic cancer. Alongside tumor cell-intrinsic mechanisms associated with oncogenic KRAS-induced inflammation, the tolerogenic myeloid cell infiltrate has emerged as a critical impediment to adaptive antitumor immune responses. Furthermore, the discovery of an intratumoral microbiome and the elucidation of host-microbe interactions that curtail antitumor immunity also present opportunities for intervention. Here we review the mechanisms of immunotherapy resistance in pancreatic ductal adenocarcinoma and discuss strategies to directly augment T cell responses in parallel with myeloid cell- and microbiome-targeted approaches that may enable immune-mediated control of this malignancy.
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