Relevance of tumor microbiome in cancer incidence,prognosis, and its clinical implications in therapeutics

The microbiota is garnering progressively greater consideration as an essential facet of the tumor microenvironment that regulates tumor proliferation and affects cancer prognosis. Microbial populations that inhabit different body locations are involved in the carcinogenesis and tumor progression of their corresponding malignancies. It has been learned that the microbial populations primarily thriving within tumors are tumor-type specific. Mechanistic studies have revealed that the tumor-associated microbiota contributes to playing a pivotal role in the establishment of the tumor microenvironment, regulation of local immunity, modulation of tumor cell biology, and directly influences the therapeutic efficacy of drug treatment for tumors. This review article incorporates the pertinent studies on recent advancements in tumor microbiome studies, the interplay between the intratumor microbiota and cancer, and, discusses their role and mechanism of action in the emergence and treatment of cancer, and their relationship to clinical characteristics.     

肠道微生物与结直肠癌

结直肠癌(colorectal cancer, CRC)是最常见的恶性肿瘤之一,严重威胁着人类健康。肠道微生态作为人体内最复杂、最庞大的微生态系统,与CRC密切相关。CRC患者的肠道微生物群落多样性构成能调节CRC疾病的发生与发展。本综述旨在讨论CRC肠道微生物群的构成、微生物群相关致癌机制、微生物群作为CRC生物标志物的潜力,为临床应用肠道菌群治疗CRC提供新策略与新思路。     

Unexpected guests in the tumor microenvironment:microbiome in cancer

Although intestinal microbiome have been established as an important biomarker and regulator of cancer development and therapeutic response,less is known about the role of microbiome at other body sites in cancer.Emerging evidence has revealed that the local microbiota make up an important part of the tumor microenvironment across many types of cancer,espe-cially in cancers arising from mucosal sites,including the lung,skin and gastrointestinal tract.The populations of bacteria that reside specifically within tumors have been found to be tumor-type specific,and mechanistic studies have demonstrated that tumor-associated microbiota may directly regulate cancer initiation,pro-gression and responses to chemo-or immuno-thera-pies.This review aims to provide a comprehensive review of the important literature on the microbiota in the cancerous tissue,and their function and mechanism of action in cancer development and treatment.     

Gut microbiome and cancer implications: Potential opportunities for fermented foods

There is a critical opportunity to improve response to immunotherapies and overall cancer survivorship via dietary interventions targeted to modify the gut microbiome, and in turn, potentially enhance anti-cancer immunity. A promising dietary intervention is fermented foods, which may alter gut microbiome composition and, in turn, improve immunity. In this article, we summarize the state of the literature pertaining to the gut microbiome and response to immunotherapy and other cancer treatments, potential clinical implications of utilizing a fermented foods dietary approach to improve cancer treatment outcomes, and existing gaps in the literature regarding the implementation of fermented food interventions among individuals with cancer or with a history of cancer. This review synthesizes a compelling rationale across different disciplines to lay a roadmap for future fermented food dietary intervention research aimed at modulating the gut microbiome to reduce cancer burden.     

Gut microbiome and cancer immunotherapy

Gut microbiome has received significant attention for its influences on a variety of host functions, especially immune modulation. With the next-generation sequencing methodologies, more knowledge is gathered about gut microbiome and its irreplaceable role in keeping the balance between human health and diseases is figured out. Immune checkpoint inhibitors (ICIs) are one of the most innovational cancer immunotherapies across cancer types and significantly expand the therapeutic options of cancer patients. However, a proportion of patients show no effective responses or develop immune-related adverse events when responses do occur. More important, it is demonstrated that the therapeutic response or treatment-limiting toxicity of cancer immunotherapy can be ameliorated or diminished by gut microbiome modulation. In this review, we first introduce the relationship between gut microbiome and cancer immunotherapy. And then, we expound the impact of gut microbiome on efficacy and toxicity of cancer immunotherapy. Further, we review approaches to manipulating gut microbiome to regulate response to ICIs. Finally, we discuss the current challenges and propose future directions to improve cancer immunotherapy via gut microbiome manipulation.     

肺部微生物组通过炎症反应介导慢性阻塞性肺疾病转化为肺癌的研究进展

肺部微生物组存在于呼吸道和实质组织中,通过菌群紊乱、代谢产物、炎症反应、免疫反应、基因毒性等方面介导肺部损伤。随着肺部微生物组的深入研究,发现肺部微生物组的相关活动与慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)和肺癌息息相关,能够促使COPD向肺癌的转变。本文主要介绍了肺部微生物组稳态及其通过炎症反应导致COPD和肺癌,重点探讨了肺部微生物组如何通过炎症反应介导COPD转化为肺癌,以期为COPD和肺癌的临床预防、优化治疗以及新型药物设计提供新的理论依据。     

Gut microbiome in tumorigenesis and therapy of colorectal cancer

Colorectal cancer (CRC) is the malignant tumor with the highest incidence in the digestive system, and the gut microbiome plays a crucial role in CRC tumorigenesis and therapy. The gastrointestinal tract is the organ harboring most of the microbiota in humans. Changes in the gut microbiome in CRC patients suggest possible host–microbe interactions, thereby hinting the potential tumorigenesis, which provides new perspective for preventing, diagnosing, or treating CRC. In this review, we discuss the effects of gut microbiome dysbiosis on CRC, and reveal the mechanisms by which gut microbiome dysbiosis leads to CRC. Gut microbiome modulation with the aim to reverse the established gut microbial dysbiosis is a novel strategy for the prevention and treatment of CRC. In addition, this review summarizes that probiotic antagonize CRC tumorigenesis by protecting intestinal barrier function, inhibiting cancer cell proliferation, resisting oxidative stress, and enhancing host immunity. Finally, we highlight clinical applications of the gut microbiome, such as gut microbiome analysis-based biomarker screening and prediction, and microbe modulation-based CRC prevention, treatment enhancement, and treatment side effect reduction. This review provides the reference for the clinical application of gut microbiome in the prevention and treatment of CRC.     

肠道菌群与结核病之间相关性的研究进展

随着新一代测序技术的发展,肠道菌群成为生物学研究领域的一大热点,特别是肠道菌群与人体各种疾病之间的关系受到广泛关注。目前已有研究发现结核分枝杆菌感染会引起肠道菌群改变,而肠道菌群失调也会增加机体对结核分枝杆菌的易感性,两者通过机体免疫反应、菌群代谢产物等因素相互影响。本文就肠道菌群与结核病的关系、肠道菌群与结核病相互影响的可能机制、抗结核治疗对肠道菌群的影响等方面的相关研究进行综述。     

Prognostic value of mutations in TP53 and RAS genes in breast cancer

The identification of molecular indicators of higher risk for specific subgroups of cancer patients may allow to develop more aggressive therapeutic strategies aimed at cases with the highest likelihood of response. This would avoid unnecessary toxicity to patients and alleviate the burden of cancer care for healthcare systems. Activated oncogenes and mutated tumor suppressor genes are causal determinants of the appearance and progression of tumors in man. They therefore represent potential indicators of prognosis and/or response to therapy. However, even in cases of well-studied oncogenes and tumor suppressor genes such as TP53 and RAS, their attributed prognostic and predictive value is often based on studies of insufficient statistical power that often lead to conflicting conclusions. Findings in favor or against the use of TP53 and RAS as prognostic and predictive indicators in breast cancer are reviewed and discussed here.     

Gut microbiome in cancer immunotherapy: Current trends,translational challenges and future possibilities

Gut microbiota is regarded as a crucial regulator of the immune system. Healthy gut microbiota plays a specialized role in host xenobiotics, nutrition, drug metabolism, regulation of the structural integrity of the gut mucosal barrier, defense against infections, and immunomodulation. It is now understood that any imbalance in gut microbiota composition from that present in a healthy state is linked to genetic susceptibility to a number of metabolic disorders, including diabetes, autoimmunity, and cancer. Recent research has suggested that immunotherapy can treat many different cancer types with fewer side effects and better ability to eradicate tumors than conventional chemotherapy or radiotherapy. However, a significant number of patients eventually develop immunotherapy resistance. A strong correlation was observed between the composition of the gut microbiome and the effectiveness of treatment by examining the variations between populations that responded to immunotherapy and those that did not. Therefore, we suggest that modulating the microbiome could be a potential adjuvant therapy for cancer immunotherapy and that the architecture of the gut microbiota may be helpful in explaining the variation in treatment response. Herein, we focus on recent research on the interactions among the gut microbiome, host immunity, and cancer immunotherapy. In addition, we highlighted the clinical manifestations, future opportunities, and limitations of microbiome manipulation in cancer immunotherapy.     

Current perspectives in cancer proteomics

Proteome technology has been used widely in cancer research and is a useful tool for the identification of new cancer markers and treatment-related changes in cancer. This article details the use of proteome technology in cancer research, and laboratory-based and clinical cancer research studies are described. New developments in proteome technology that enable higher sample-throughput are evaluated and methods for enhancing conventional proteome analysis (based on two-dimensional electrophoresis) discussed. The need to couple laboratory-based proteomics research with clinically relevant models of the disease is also considered, as this remains the next main challenge of cancer-related proteome research.     

肠道微生物组与宿主的表观遗传修饰

高通量测序技术已经增加了人们对肠道微生物组和表观遗传学修饰的理解,将肠道微生物组和宿主表观遗传学修饰紧密联系起来,阐明了很多疾病的发生过程如免疫、代谢、心血管疾病甚至是癌症。肠道微生物组与宿主具有相互作用,与人体密不可分,相辅相成。肠道微生物组的生态失调可能诱导疾病的发生并能调控宿主表观遗传学修饰。宿主表观遗传学调控和肠道微生物组(或其代谢产物)变化的相互关系在很多疾病中都有报道。因此,肠道微生物组可作为某些疾病的诊断标记,健康肠道微生物组的移植会逆转这种微生态失调,可作为一种有效的治疗策略。本文主要探讨了肠道微生物组直接调控宿主表观修饰和通过小分子生物活性物质和其他酶辅因子间接影响表观修饰,以及基于肠道微生物组调控宿主表观修饰的诊断和治疗应用等。     

Analyzing the Secretome of Gut Microbiota as the Next Strategy For Early Detection of Colorectal Cancer

Dysbiosis of gut microbiome can contribute to inflammation, and subsequently initiation and progression of colorectal cancer (CRC). Throughout these stages, various proteins and metabolites are secreted to the external environment by microorganisms or the hosts themselves. Studying these proteins may help enhance our understanding of the host–microorganism relationship or they may even serve as useful biomarkers for CRC. However, secretomic studies of gut microbiome of CRC patients, until now, are scarcely performed. In this review article, the focus is on the roles of gut microbiome in CRC, the current findings on CRC secretome are highlighted, and the emerging challenges and strategies to drive forward this area of research are addressed.     

Biomarkers for prostate cancer

The detection of prostate cancer using a blood test has by many standards changed the face of the disease. Despite this tremendous success, there are limitations attributed to the use of prostate specific antigen (PSA) as a means to screen and detect prostate cancer. PSA, as its name implies, is not specific for prostate cancer and as such is often found elevated in other prostatic diseases/symptoms associated with the aging male. Clearly, more specific marker(s) that could identify which individuals actually have prostate cancer and differentiate them from those without the disease would be of tremendous value. The search for more accurate and clinically useful biomarkers of prostate cancer has been extensive. This has focused on individual markers, as well as groups of markers. Included among these are PSA isoforms, pathological indicators and stains, nucleic acids and others. This article highlights the discovery of PSA as a first blood‐based biomarker for prostate cancer detection, as well as other molecular biomarkers and their potential application in detection of the disease. J. Cell. Biochem. 108: 3–9, 2009. © 2009 Wiley‐Liss, Inc.     

结直肠癌与肠道微生物群研究进展

肠道微生物群是人体内环境的重要组成部分,与宿主共进化、共代谢、共发育,并与宿主之间相互调控,影响宿主健康。近年研究显示,肠道微生物群参与了结直肠癌的发生和发展。了解肠道微生物群的特征性变化及其诱发结直肠癌的机制对于结直肠癌的防治有着重要意义。目前以肠道微生物群为靶点的干预性基础研究也取得了一些突破性的研究进展。本文主要对结直肠癌患者肠道微生物群的变化、其可能的致病机制及临床相关研究进展等进行综述。     

Cyclooxygenase-2 and chemoprevention of breast cancer

This article discusses the role of cycclooxygenase-2 (COX-2) in the aetiology and progression of breast cancer. Renewed interest in chemoprevention using non-steroidal antiinflammatory drugs (NSAIDS) has come from observations that regular NSAID use is associated with a reduced incidence of some cancers including that of the breast. There is an increasing body of evidence supporting a role for COX-2 in breast cancer development and progression via effects on angiogenesis and apoptosis as well as via effects on intratumoural aromatase. New selective inhibitors of COX-2 are currently licensed for use in the treatment of arthritis and more recently in the chemoprevention of familial adenomatous polyposis (FAP). Large clinical chemoprevention studies with COX-2 inhibitors are already underway in colorectal cancer. Their role in breast cancer prevention and treatment has yet to be fully characterised, but merits further investigation.     

Public human microbiome data are dominated by highly developed countries

The importance of sampling from globally representative populations has been well established in human genomics. In human microbiome research, however, we lack a full understanding of the global distribution of sampling in research studies. This information is crucial to better understand global patterns of microbiome-associated diseases and to extend the health benefits of this research to all populations. Here, we analyze the country of origin of all 444,829 human microbiome samples that are available from the world’s 3 largest genomic data repositories, including the Sequence Read Archive (SRA). The samples are from 2,592 studies of 19 body sites, including 220,017 samples of the gut microbiome. We show that more than 71% of samples with a known origin come from Europe, the United States, and Canada, including 46.8% from the US alone, despite the country representing only 4.3% of the global population. We also find that central and southern Asia is the most underrepresented region: Countries such as India, Pakistan, and Bangladesh account for more than a quarter of the world population but make up only 1.8% of human microbiome samples. These results demonstrate a critical need to ensure more global representation of participants in microbiome studies.

The importance of sampling from globally representative populations has been well established in human genomics, but what about the microbiome? This study shows that metadata from almost half a million samples reveals worldwide human microbiome research is skewed heavily in favor of Europe and North America and excludes large but less developed nations in Asia and Africa.     

The potential for probiotic manipulation of the gastrointestinal microbiome

Multiple internal and external sites of the healthy human body are colonized by a diversity of symbiotic microbes. The microbial assemblages found in the intestine represent some of the most dense and diverse of these human-associated ecosystems. Unsurprisingly, the enteric microbiome, that is the totality of microbes, their combined genomes, and their interactions with the human body, has a profound impact on physiological aspects of mammalian function, not least, host immune response. Lack of early-life exposure to certain microbes, or shifts in the composition of the gastrointestinal microbiome have been linked to the development and progression of several intestinal and extra-intestinal diseases, including childhood asthma development and inflammatory bowel disease. Modulating microbial exposure through probiotic supplementation represents a long-held strategy towards ameliorating disease via intestinal microbial community restructuring. This field has experienced somewhat of a resurgence over the past few years, primarily due to the exponential increase in human microbiome studies and a growing appreciation of our dependence on resident microbiota to modulate human health. This review aims to review recent regulatory aspects related to probiotics in food. It also summarizes what is known to date with respect to human gastrointestinal microbiota - the niche which has been most extensively studied in the human system - and the evidence for probiotic supplementation as a viable therapeutic strategy for modulating this consortium.     

Proteogenomics meets cancer immunology: mass spectrometric discovery and analysis of neoantigens

Cancer proteogenomics is an emerging field that aims to identify and quantify protein sequence changes associated with the cancer genome. Besides being involved in cancer development and progression, such protein variants may serve as neoantigens, which provide the T-cell response against tumors. Mass spectrometry-based proteogenomics may be a promising tool for finding neoantigens in individual specimens. It is partly based on a technical background accumulated from mass spectrometric studies of peptide ligands of major histocompatibility complex proteins. Examples of the use of mass spectrometry in neoantigen identification are reviewed in this article. Some experimental workflows are discussed, which may use shotgun and targeted proteomics for translational human studies of neoepitopes, such as cancer vaccine development and checkpoint therapy response prediction.     

Signifying the Pandemics: Metaphors of AIDS, Cancer, and Heart Disease

This article offers a symbolic analysis of the cultural construction and signification of three of the major "pandemics" of the late 20th century: AIDS, cancer, and heart disease. It is based on unstructured interviews conducted in Israel between 1993–94 with 75 nurses and 40 physicians and between 1993–95 with 60 university students. Two key symbols, "pollution" and "transformation" are shown to constitute AIDS and cancer within a symbolic space that I suggest is "beyond culture" where body boundaries are dissolved and cultural categories are dismantled. Heart disease, in contrast, is metaphorized as a defect in the "body machinery." The article concludes by arguing that heart attack is depicted as the pathology of the Fordist, modernist body, while AIDS/cancer are pathologies of the postmodern body in late capitalism. [AIDS, cancer, heart disease, semiotics, metaphorization]