From the Ella Lemelbaum institute for immuno-oncology and melanoma, Sheba Medical Center, Ramat Gan.
Tel-Aviv University, Tel-Aviv.
Cancer J. 2023;29(2):102-108. doi: 10.1097/PPO.0000000000000651.
For decades, cancer research and treatment focused on the cellular level, viewing cancer as a genetic disease of cell transformation. In the era of chemotherapy and radiotherapy, studies from the second half of the 19th century suggesting an association between the microbiota and cancer were almost neglected. The main focus of the field was limited to identification of specific viruses and bacteria that may serve as direct carcinogens leading to the recognition of 7 viruses (i.e., human papillomavirus, hepatitis B virus, and Kaposi sarcoma-associated herpesvirus) and 1 bacterium (Helicobacter pylori) as human carcinogens by the International Agency for Research on Cancer (https://monographs.iarc.who.int/agents-classified-by-the-iarc/). Shortly after the publication of the first draft of the human genome project in February 2001, the Nobel laureate microbiologist Joshua Lederberg raised the question: "Is human identity all in the genes?" It took more than a decade later and the development of multiomic techniques to confirm that his answer "each one of us is a small ecological community" was correct (Lederberg J. Keynote Address: Beyond the Genome. Brooklyn Law Rev 67). This ecological notion became relevant to cancer prevention, prediction, and treatment following the immunotherapy revolution and the understanding of the metabolic and immunologic roles of the microbiota in health and disease. Recently, the microbiota was recognized as an emerging hallmark of cancer following a large body of research showing its role in tumorigenesis, treatment efficacy and toxicity, and initial data regarding the role of microbial modulation in cancer therapy (Cancer Discov 2022;12(1):31-46). In the current review, we will focus on the role of fecal microbiota transplantation, the first microbial modulation technique that is used mainly in low-complexity conditions such as recurrent Clostridium difficile infections (Aliment Pharmacol Ther 2017;46(5):479-493), as a possible cancer therapeutic. However, to better understand the suggested roles of fecal microbiota transplantation in medical oncology, we first need to understand cancer as an ecological niche and the role of the microbiota in tumorigenesis and cancer treatment, specifically immunotherapy.
几十年来，癌症研究和治疗一直专注于细胞水平，将癌症视为细胞转化的遗传疾病。在化疗和放疗时代，19 世纪后半叶的研究表明微生物组与癌症之间存在关联，但这些研究几乎被忽视。该领域的主要关注点仅限于识别可能作为直接致癌剂的特定病毒和细菌，这导致国际癌症研究机构 (International Agency for Research on Cancer，IARC) 认识到 7 种病毒（即人乳头瘤病毒、乙型肝炎病毒和卡波西肉瘤相关疱疹病毒）和 1 种细菌（幽门螺杆菌）为人类致癌剂 (https://monographs.iarc.who.int/agents-classified-by-the-iarc/)。在 2001 年 2 月首次公布人类基因组计划初稿后不久，诺贝尔奖获得者微生物学家 Joshua Lederberg 提出了一个问题：“人类的身份是否全在基因里？”直到 10 多年后，随着多组学技术的发展，他的答案“我们每个人都是一个小型生态群落”才得到证实（Lederberg J. Keynote Address: Beyond the Genome. Brooklyn Law Rev 67）。在免疫治疗革命以及对微生物在健康和疾病中的代谢和免疫作用的理解之后，这种生态概念与癌症的预防、预测和治疗相关。最近，大量研究表明微生物组在肿瘤发生、治疗效果和毒性中的作用，以及关于微生物调节在癌症治疗中的作用的初步数据，微生物组被认为是癌症的一个新特征标志（Cancer Discov 2022;12(1):31-46）。在本综述中，我们将重点关注粪便微生物群移植的作用，粪便微生物群移植是第一种主要用于复发性艰难梭菌感染等低复杂性条件下的微生物调节技术（Aliment Pharmacol Ther 2017;46(5):479-493），作为一种潜在的癌症治疗方法。然而，为了更好地理解粪便微生物群移植在肿瘤学中的作用，我们首先需要将癌症视为一个生态位，以及微生物组在肿瘤发生和癌症治疗（特别是免疫治疗）中的作用。
