Microbiota-metabolism-epigenetics-immunity axis in cancer - Opinion

Sep 21, 2026

Uploaded by Noah

Open-access opinion article published in Frontiers in Immunology presents cancer as an interrelated disease network shaped by the hallmarks of cancer, including immune evasion and nonmutational epigenetic reprogramming. It focuses on how gut microbiota can modulate immune-checkpoint blockade by fine-tuning antitumor immunity and, in some cases, hindering immune responses. The work also highlights microbiota-derived metabolites and metabolic-epigenetic crosstalk, linking host urea cycle dysregulation and acetyl-CoA-driven histone acetylation to tumor development, emphasizing integrated cancer biology.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages4

Reading Time10 min

AccessFree to download

Introduction

From microbiota to immunity

TYPE Opinion PUBLISHED 12 July 2024 DOI 10.3389/fimmu.2024.1449912 OPEN ACCESS EDITED BY John Stewart, Morehouse School of Medicine, United States REVIEWED BY Weiliang Hou, Tongji University, China *CORRESPONDENCE Lei You ﬂ[orayo@163.com](orayo@163.com)[ ](orayo@163.com)Taiping Zhang [tpingzhang@yahoo.com](tpingzhang@yahoo.com)[ ](tpingzhang@yahoo.com)Yupei Zhao [zhao8028@263.net](zhao8028@263.net) RECEIVED 16 June 2024 ACCEPTED 03 July 2024 PUBLISHED 12 July 2024 CITATION Ren B, Fang Y, Gu M, You L, Zhang T and Zhao Y (2024) Microbiota-metabolismepigenetics-immunity axis in cancer. Front. Immunol. 15:1449912 . doi: 10.3389/fimmu.2024.1449912 COPYRIGHT © 2024 Ren, Fang, Gu, You, Zhang and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Microbiota-metabolismepigenetics-immunity axis in cancer Bo Ren 1,2,3, Yuan Fang 1,2,3, Minzhi Gu 1,2,3, Lei You 1,2,3*, Taiping Zhang 1,2,3* and Yupei Zhao 1,2,3* 1 Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China, 2 Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing, China, 3 National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Beijing, China KEYWORDS immunotherapy, microbiota, metabolism, epigenetics, hallmarks of cancer Introduction Over the past several years, the ﬁeld of oncology has seen rapid advances, generating a comprehensive and intricate understanding of cancer. This body of knowledge has unveiled cancer as a disease characterized by ongoing transformations across various physiological and pathological processes. Based on these researches and ﬁndings, the hallmarks of cancer have been delineated, providing a collection of essential functional attributes that human cells undergo during their transition from a healthy state to a state of cancerous proliferation. These attributes are pivotal for the cells’ capacity to initiate and sustain the growth of malignant tumors. As of the latest updates, Prof. Hanahan and Weinberg have identiﬁed a total of 14 hallmarks that characterize cancer (1–3) . These hallmarks encompass a range of cellular capabilities and adaptations, including sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, and activating invasion & metastasis. They also address the tumor’s interaction with the microenvironment, such as promoting genome instability & mutation, inducing tumor-promoting inﬂammation, and deregulating cellular metabolism. Furthermore, they highlight the importance of avoiding immune destruction, unlocking phenotypic plasticity, undergoing nonmutational epigenetic reprogramming, and engaging with polymorphic microbiomes, as well as the role ofsenescent cells in cancer development. Contrary to once being viewed as discrete, the hallmarks of cancer are now recognized as interrelated and mutually reinforcing processes. The intricate crosstalk between these hallmarks is the subject of intense investigation, as elucidating their complex interactions holds the key to understanding cancer’s adaptability and resistance to therapies. For instance, research has highlighted that the gut microbiota has the capacity to both amplify the beneﬁts of immunotherapy by ﬁne-tuning the body’s antitumor immune response via checkpoint inhibitors (4, 5), and also, in some cases, to impede the immune system’s ability to ﬁght off cancer (6), under

FAQs

What is the article’s central focus regarding cancer biology?

It emphasizes the microbiota-metabolism-epigenetics-immunity axis and how these processes interact with the broader hallmarks of cancer to shape tumor development, adaptability, and therapy resistance.

How can gut microbiota affect immune checkpoint blockade therapy?

Gut microbiota can amplify immunotherapy benefits by tuning antitumor immune responses through checkpoint inhibitors, while some findings also indicate microbiota may impede the immune system’s ability to fight cancer.

What metabolic and epigenetic mechanisms are highlighted in relation to tumors?

The text describes maladaptation of host–microbiota metabolic interaction, including urea cycle metabolism dysregulation in colorectal cancer, and acetyl-CoA–linked histone acetylation driven by pancreatic KRAS mutations, connecting metabolism with nonmutational epigenetic reprogramming.

Sep 21, 2026

Uploaded by Noah