免疫抑制
肿瘤微环境
背景(考古学)
胰腺癌
生物
癌症
癌症研究
免疫学
免疫系统
遗传学
古生物学
作者
Chiara Falcomatà,Stefanie Bärthel,Günter Schneider,Roland Rad,Marc Schmidt-Supprian,Dieter Saur
出处
期刊:Cancer Discovery
[American Association for Cancer Research]
日期:2023-01-09
卷期号:13 (2): 278-297
被引量:39
标识
DOI:10.1158/2159-8290.cd-22-0876
摘要
Abstract Immunotherapies have shown benefits across a range of human cancers, but not pancreatic ductal adenocarcinoma (PDAC). Recent evidence suggests that the immunosuppressive tumor microenvironment (TME) constitutes an important roadblock to their efficacy. The landscape of the TME differs substantially across PDAC subtypes, indicating context-specific principles of immunosuppression. In this review, we discuss how PDAC cells, the local TME, and systemic host and environmental factors drive immunosuppression in context. We argue that unraveling the mechanistic drivers of the context-specific modes of immunosuppression will open new possibilities to target PDAC more efficiently by using multimodal (immuno)therapeutic interventions. Significance: Immunosuppression is an almost universal hallmark of pancreatic cancer, although this tumor entity is highly heterogeneous across its different subtypes and phenotypes. Here, we provide evidence that the diverse TME of pancreatic cancer is a central executor of various different context-dependent modes of immunosuppression, and discuss key challenges and novel opportunities to uncover, functionalize, and target the central drivers and functional nodes of immunosuppression for therapeutic exploitation.
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