Fusobacterium nucleatum outer membrane vesicles activate autophagy to promote oral cancer metastasis DOI Creative Commons

Gang Chen,

Chunna Gao,

Shan Jiang

et al.

Journal of Advanced Research, Journal Year: 2023, Volume and Issue: 56, P. 167 - 179

Published: April 13, 2023

Metastasis is an important cause of high mortality and lethality oral cancer. Fusobacterium nucleatum (Fn) can promote tumour metastasis. Outer membrane vesicles (OMVs) are secreted by Fn. However, the effects Fn-derived extracellular on cancer metastasis underlying mechanisms unclear. We aimed to determine whether how Fn OMVs mediate were isolated from brain heart infusion (BHI) broth supernatant ultracentrifugation. Tumour-bearing mice treated with evaluate effect Transwell assays performed affect cell migration invasion. The differentially expressed genes in OMV-treated/untreated cells identified RNA-seq. Transmission electron microscopy, laser confocal lentiviral transduction used detect changes autophagic flux stimulated OMVs. Western blotting assay was EMT-related marker protein levels cells. OMVs' after blocking autophagy inhibitors determined vitro vivo experiments. structurally similar vesicles. In experiment, promoted lung tumour-bearing mice, while chloroquine (CHQ, inhibitor) treatment reduced number pulmonary metastases resulting intratumoral OMV injection. invasion vivo, leading altered expression proteins (E-cadherin downregulation; Vimentin/N-cadherin upregulation). RNA-seq showed that activate intracellular pathways. Blocking CHQ induced as well reversed expression. not only but also activated flux. weakened OMV-stimulated

Language: Английский

Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer DOI Creative Commons
Jorge Luis Galeano Niño, Hanrui Wu, Kaitlyn D. LaCourse

et al.

Nature, Journal Year: 2022, Volume and Issue: 611(7937), P. 810 - 817

Published: Nov. 16, 2022

Abstract The tumour-associated microbiota is an intrinsic component of the tumour microenvironment across human cancer types 1,2 . Intratumoral host–microbiota studies have so far largely relied on bulk tissue analysis 1–3 , which obscures spatial distribution and localized effect within tumours. Here, by applying in situ spatial-profiling technologies 4 single-cell RNA sequencing 5 to oral squamous cell carcinoma colorectal cancer, we reveal spatial, cellular molecular host–microbe interactions. We adapted 10x Visium transcriptomics determine identity location intratumoral microbial communities patient tissues. Using GeoMx digital profiling 6 show that bacterial populate microniches are less vascularized, highly immuno‑suppressive associated with malignant cells lower levels Ki-67 as compared bacteria-negative regions. developed a RNA-sequencing method name INVADEseq (invasion–adhesion-directed expression sequencing) and, this tumours, identify cell-associated bacteria host they interact, well uncovering alterations transcriptional pathways involved inflammation, metastasis, dormancy DNA repair. Through functional studies, infected invade their surrounding environment single recruit myeloid Collectively, our data not random; instead, it organized immune epithelial functions promote progression.

Language: Английский

Citations

455
Metastasis DOI Creative Commons

Stefanie Gerstberger,

Qingwen Jiang, Karuna Ganesh

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(8), P. 1564 - 1579

Published: April 1, 2023

Language: Английский

Citations

357
Dietary tryptophan metabolite released by intratumoral Lactobacillus reuteri facilitates immune checkpoint inhibitor treatment DOI Creative Commons
Mackenzie Bender,

Alex McPherson,

Catherine M. Phelps

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(9), P. 1846 - 1862.e26

Published: April 1, 2023

Language: Английский

Citations

319
Intratumoral microbiota: roles in cancer initiation, development and therapeutic efficacy DOI Creative Commons
Yang Li,

Aitian Li,

Ying Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Jan. 16, 2023

Abstract Microorganisms, including bacteria, viruses, fungi, and other eukaryotes, play critical roles in human health. An altered microbiome can be associated with complex diseases. Intratumoral microbial components are found multiple tumor tissues closely correlated cancer initiation development therapy efficacy. The intratumoral microbiota may contribute to promotion of the progression cancers by DNA mutations, activating carcinogenic pathways, promoting chronic inflammation, complement system, initiating metastasis. Moreover, not only enhance antitumor immunity via mechanisms STING signaling activation, T NK cell TLS production, microbiota-derived antigen presenting, but also decrease immune responses promote through pathways upregulation ROS, an anti-inflammatory environment, inactivation, immunosuppression. effect on is dependent composition, crosstalk between cancer, status cancers. regulate physiology response different β-catenin, TLR, ERK, NF-κB, STING, among others. These viewpoints help identify as diagnosis or prognosis evaluation cancers, new therapeutic strategy potential targets for therapy.

Language: Английский

Citations

196
Role of the gut microbiota in anticancer therapy: from molecular mechanisms to clinical applications DOI Creative Commons
Lin-Yong Zhao,

Jia-Xin Mei,

Gang Yu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 13, 2023

Abstract In the past period, due to rapid development of next-generation sequencing technology, accumulating evidence has clarified complex role human microbiota in cancer and therapeutic response. More importantly, available seems indicate that modulating composition gut improve efficacy anti-cancer drugs may be feasible. However, intricate complexities exist, a deep comprehensive understanding how interacts with is critical realize its full potential treatment. The purpose this review summarize initial clues on molecular mechanisms regarding mutual effects between development, highlight relationship microbes immunotherapy, chemotherapy, radiation therapy surgery, which provide insights into formulation individualized strategies for management. addition, current emerging microbial interventions as well their clinical applications are summarized. Although many challenges remain now, great importance cannot overstated strategies, it necessary explore holistic approach incorporates modulation cancer.

Language: Английский

Citations

159
Bacteria in cancer initiation, promotion and progression DOI
Geniver El Tekle, Wendy S. Garrett

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(9), P. 600 - 618

Published: July 3, 2023

Language: Английский

Citations

156
Inflammation: the incubator of the tumor microenvironment DOI
Dominic Denk, Florian R. Greten

Trends in cancer, Journal Year: 2022, Volume and Issue: 8(11), P. 901 - 914

Published: July 28, 2022

Language: Английский

Citations

153
Targeting the gut microbiota for cancer therapy DOI
Miriam R. Fernandes, Poonam Aggarwal, Raquel Costa

et al.

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(12), P. 703 - 722

Published: Oct. 17, 2022

Language: Английский

Citations

149
Antigen presentation in cancer — mechanisms and clinical implications for immunotherapy DOI
Kailin Yang, Ahmed Halima, Timothy A. Chan

et al.

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(9), P. 604 - 623

Published: June 16, 2023

Language: Английский

Citations

115
Association of Intratumoral Microbiota With Prognosis in Patients With Nasopharyngeal Carcinoma From 2 Hospitals in China DOI Creative Commons
Han Qiao,

Xi-Rong Tan,

Hui Li

et al.

JAMA Oncology, Journal Year: 2022, Volume and Issue: 8(9), P. 1301 - 1301

Published: July 14, 2022

Microbiota-tumor interactions have qualified microbiota as a promising prognostic biomarker in various types of cancers. Although the nasopharynx acts crucial niche upper respiratory tract microbiome, whether intratumoral exists and its clinical significance nasopharyngeal carcinoma (NPC) remain uncertain.To evaluate for individual prognostication patients with NPC.This retrospective cohort study included NPC biopsy samples from 2 hospitals: Sun Yat-sen University Cancer Center (Guangzhou, China) Zhejiang Hospital (Hangzhou, between January 2004 November 2016, follow-up through 2020. A total 802 were according to following criteria: histologically proven NPC, without distant metastasis at initial diagnosis, had not received antitumor treatment before sampling, aged 18 70 years, complete medical records regular follow-up, history cancer, successfully extracted enough DNA experiments.The primary end point was disease-free survival, secondary points metastasis-free survival overall survival. To assess existence load 96 or tumor relapse, 16S rRNA sequencing quantitative polymerase chain reaction used. The associations bacterial outcome evaluated 241 fresh-frozen (training cohort) validated paraffin-embedded internal (n = 233) external 232) validation cohorts. Metagenomic transcriptome analyses performed ascertain origin underlying mechanism bacteria.A (mean [SD] age, 46.2 [10.6] years; 594 [74.1%] male) enrolled. Microbiota presented within tissues, among which Corynebacterium Staphylococcus predominated. Patients high training inferior rates (hazard ratio [HR], 2.90; 95% CI, 1.72-4.90; P < .001), (HR, 3.18; 1.58-6.39; 3.41; 1.90-6.11, .001) than those low load, finding that by Single-nucleotide variant analysis revealed main bacteria. Transcriptome digital pathology demonstrated higher negatively associated T-lymphocyte infiltration.Intratumoral robust tool this study, indicating potential guidance decisions different levels risk malignant progression.

Language: Английский

Citations

93