The microbiome-derived metabolite TMAO drives immune activation and boosts responses to immune checkpoint blockade in pancreatic cancer DOI
Gauri Mirji,

Alison Worth,

Sajad A. Bhat

и другие.

Science Immunology, Год журнала: 2022, Номер 7(75)

Опубликована: Сен. 9, 2022

The composition of the gut microbiome can control innate and adaptive immunity has emerged as a key regulator tumor growth, especially in context immune checkpoint blockade (ICB) therapy. However, underlying mechanisms for how affects growth remain unclear. Pancreatic ductal adenocarcinoma (PDAC) tends to be refractory therapy, including ICB. Using nontargeted, liquid chromatography–tandem mass spectrometry–based metabolomic screen, we identified microbe–derived metabolite trimethylamine N -oxide (TMAO), which enhanced antitumor PDAC. Delivery TMAO intraperitoneally or via dietary choline supplement orthotopic PDAC-bearing mice reduced associated with an immunostimulatory tumor-associated macrophage (TAM) phenotype, activated effector T cell response microenvironment. Mechanistically, potentiated type I interferon (IFN) pathway conferred effects IFN–dependent manner. Delivering TMAO-primed macrophages intravenously produced similar effects. Combining ICB (anti-PD1 and/or anti-Tim3) mouse model PDAC significantly burden improved survival beyond alone. Last, levels bacteria containing CutC (an enzyme that generates trimethylamine, precursor) correlated long-term patients anti-PD1 melanoma. Together, our study identifies microbial driver lays groundwork potential therapeutic strategies targeting TMAO.

Язык: Английский

Hallmarks of Cancer: New Dimensions DOI Open Access
Douglas Hanahan

Cancer Discovery, Год журнала: 2022, Номер 12(1), С. 31 - 46

Опубликована: Янв. 1, 2022

The hallmarks of cancer conceptualization is a heuristic tool for distilling the vast complexity phenotypes and genotypes into provisional set underlying principles. As knowledge mechanisms has progressed, other facets disease have emerged as potential refinements. Herein, prospect raised that phenotypic plasticity disrupted differentiation discrete hallmark capability, nonmutational epigenetic reprogramming polymorphic microbiomes both constitute distinctive enabling characteristics facilitate acquisition capabilities. Additionally, senescent cells, varying origins, may be added to roster functionally important cell types in tumor microenvironment. SIGNIFICANCE: Cancer daunting breadth scope its diversity, spanning genetics, tissue biology, pathology, response therapy. Ever more powerful experimental computational tools technologies are providing an avalanche "big data" about myriad manifestations diseases encompasses. integrative concept embodied helping distill this increasingly logical science, new dimensions presented perspective add value endeavor, fully understand development malignant progression, apply medicine.

Язык: Английский

Процитировано

3364

Systemic immunity in cancer DOI Open Access
Kamir J. Hiam-Galvez, Breanna M. Allen, Matthew H. Spitzer

и другие.

Nature reviews. Cancer, Год журнала: 2021, Номер 21(6), С. 345 - 359

Опубликована: Апрель 9, 2021

Язык: Английский

Процитировано

1004

The microbiome and human cancer DOI
Gregory D. Sepich‐Poore, Laurence Zitvogel, Ravid Straussman

и другие.

Science, Год журнала: 2021, Номер 371(6536)

Опубликована: Март 25, 2021

Microbial roles in cancer formation, diagnosis, prognosis, and treatment have been disputed for centuries. Recent studies provocatively claimed that bacteria, viruses, and/or fungi are pervasive among cancers, key actors immunotherapy, engineerable to treat metastases. Despite these findings, the number of microbes known directly cause carcinogenesis remains small. Critically evaluating building frameworks such evidence light modern biology is an important task. In this Review, we delineate between causal complicit trace common themes their influence through host's immune system, herein defined as immuno-oncology-microbiome axis. We further review intratumoral approaches manipulate gut or tumor microbiome while projecting next phase experimental discovery.

Язык: Английский

Процитировано

898

Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms DOI
Patrice D. Cani, Clara Depommier, Muriel Derrien

и другие.

Nature Reviews Gastroenterology & Hepatology, Год журнала: 2022, Номер 19(10), С. 625 - 637

Опубликована: Май 31, 2022

Язык: Английский

Процитировано

653

Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer DOI Creative Commons
Maik Luu, Zeno Riester,

Adrian Baldrich

и другие.

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Июль 1, 2021

Abstract Emerging data demonstrate that the activity of immune cells can be modulated by microbial molecules. Here, we show short-chain fatty acids (SCFAs) pentanoate and butyrate enhance anti-tumor cytotoxic T lymphocytes (CTLs) chimeric antigen receptor (CAR) through metabolic epigenetic reprograming. We in vitro treatment CTLs CAR with increases function mTOR as a central cellular sensor, inhibits class I histone deacetylase activity. This reprogramming results elevated production effector molecules such CD25, IFN-γ TNF-α, significantly enhances antigen-specific ROR1-targeting syngeneic murine melanoma pancreatic cancer models. Our shed light onto may used for enhancing immunity. Collectively, identify two SCFAs therapeutic utility context immunotherapy.

Язык: Английский

Процитировано

425

Microbiota triggers STING-type I IFN-dependent monocyte reprogramming of the tumor microenvironment DOI Creative Commons
Khiem C. Lam, Romina E. Araya, April Huang

и другие.

Cell, Год журнала: 2021, Номер 184(21), С. 5338 - 5356.e21

Опубликована: Окт. 1, 2021

Язык: Английский

Процитировано

393

Programmable probiotics modulate inflammation and gut microbiota for inflammatory bowel disease treatment after effective oral delivery DOI Creative Commons
Jun Zhou,

Maoyi Li,

Qiufang Chen

и другие.

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Июнь 14, 2022

Abstract Reactive oxygen species (ROS) play vital roles in intestinal inflammation. Therefore, eliminating ROS the inflammatory site by antioxidant enzymes such as catalase and superoxide dismutase may effectively curb bowel disease (IBD). Here, Escherichia coli Nissle 1917 (ECN), a kind of oral probiotic, was genetically engineered to overexpress (ECN-pE) for treatment To improve bioavailability ECN-pE gastrointestinal tract, chitosan sodium alginate, effective biofilms, were used coat via layer-by-layer electrostatic self-assembly strategy. In mouse IBD model induced different chemical drugs, chitosan/sodium alginate coating (ECN-pE(C/A) 2 ) relieved inflammation repaired epithelial barriers colon. Unexpectedly, EcN-pE(C/A) could also regulate microbial communities abundance Lachnospiraceae _NK4A136 Odoribacter flora, which are important microbes maintain homeostasis. Thus, this study lays foundation development living therapeutic proteins using probiotics treat intestinal-related diseases.

Язык: Английский

Процитировано

390

Cancer stem cell–immune cell crosstalk in tumour progression DOI
Defne Bayık, Justin D. Lathia

Nature reviews. Cancer, Год журнала: 2021, Номер 21(8), С. 526 - 536

Опубликована: Июнь 8, 2021

Язык: Английский

Процитировано

387

Microbiome and cancer DOI Creative Commons
Nyssa Cullin, Camila Azevedo Antunes, Ravid Straussman

и другие.

Cancer Cell, Год журнала: 2021, Номер 39(10), С. 1317 - 1341

Опубликована: Сен. 9, 2021

Язык: Английский

Процитировано

376

Targeting the gut and tumor microbiota in cancer DOI
Elizabeth M. Park, Manoj Chelvanambi, Neal Bhutiani

и другие.

Nature Medicine, Год журнала: 2022, Номер 28(4), С. 690 - 703

Опубликована: Апрель 1, 2022

Язык: Английский

Процитировано

334