Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida.
S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York.
Gastroenterology. 2019 May;156(7):2097-2115.e2. doi: 10.1053/j.gastro.2018.12.045. Epub 2019 Feb 12.
Our understanding of the microbiome and its role in immunity, cancer initiation, and cancer progression has evolved significantly over the past century. The "germ theory of cancer" was first proposed in the early 20 century, and shortly thereafter the bacterium Helicobacter pylori, and later Fusobacterium nucleatum, were implicated in the development of gastric and colorectal cancers, respectively. However, with the development of reliable mouse models and affordable sequencing technologies, the most fascinating aspect of the microbiome-cancer relationship, where microbes undermine cancer immune surveillance and indirectly promote oncogenesis, has only recently been described. In this review, we highlight the essential role of the microbiome in immune system development and maturation. We review how microbe-induced immune activation promotes oncogenesis, focusing particularly on pancreatic carcinogenesis, and show that modulation of the microbiome augments the anti-cancer immune response and enables successful immunotherapy against pancreatic cancer.
在过去的一个世纪里,我们对微生物组及其在免疫、癌症发生和癌症进展中的作用的理解有了显著的发展。“癌症的微生物理论”最早在 20 世纪初提出,此后不久,幽门螺杆菌(Helicobacter pylori)和随后的具核梭杆菌(Fusobacterium nucleatum)分别被认为与胃癌和结直肠癌的发生有关。然而,随着可靠的小鼠模型和可负担的测序技术的发展,微生物组-癌症关系中最吸引人的方面,即微生物破坏癌症免疫监测并间接促进肿瘤发生,最近才被描述。在这篇综述中,我们强调了微生物组在免疫系统发育和成熟中的重要作用。我们回顾了微生物诱导的免疫激活如何促进肿瘤发生,特别关注胰腺癌的发生,并表明微生物组的调节增强了抗癌免疫反应,并使针对胰腺癌的免疫治疗取得成功。