Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA; email:
Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.
Annu Rev Immunol. 2020 Apr 26;38:649-671. doi: 10.1146/annurev-immunol-082019-081656. Epub 2020 Feb 10.
A plethora of experimental and epidemiological evidence supports a critical role for inflammation and adaptive immunity in the onset of cancer and in shaping its response to therapy. These data are particularly robust for gastrointestinal (GI) cancers, such as those affecting the GI tract, liver, and pancreas, on which this review is focused. We propose a unifying hypothesis according to which intestinal barrier disruption is the origin of tumor-promoting inflammation that acts in conjunction with tissue-specific cancer-initiating mutations. The gut microbiota and its products impact tissue-resident and recruited myeloid cells that promote tumorigenesis through secretion of growth- and survival-promoting cytokines that act on epithelial cells, as well as fibrogenic and immunosuppressive cytokines that interfere with the proper function of adaptive antitumor immunity. Understanding these relationships should improve our ability to prevent cancer development and stimulate the immune system to eliminate existing malignancies.
大量的实验和流行病学证据支持炎症和适应性免疫在癌症的发生和对治疗的反应中起着关键作用。这些数据对于胃肠道（GI）癌症特别有说服力，例如影响胃肠道、肝脏和胰腺的癌症，本综述就是针对这些癌症展开的。我们提出了一个统一的假说，即肠道屏障的破坏是促进肿瘤炎症的根源，这种炎症与组织特异性的癌症起始突变共同作用。肠道微生物群及其产物影响组织驻留和募集的髓样细胞，通过分泌作用于上皮细胞的促生长和存活的细胞因子以及干扰适应性抗肿瘤免疫的成纤维和免疫抑制细胞因子来促进肿瘤发生。了解这些关系应该提高我们预防癌症发展和刺激免疫系统消除现有恶性肿瘤的能力。
