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The tumor microenvironment (TME) is a complex and dynamic ecosystem that significantly influences tumor progression, immune modulation, and therapeutic response. A key component of the TME is the tumor-associated microbiota, which has emerged as an important player in cancer biology, affecting tumor metastasis, immune evasion, and resistance to treatments. The recent advent of high-throughput sequencing technologies has revolutionized our understanding of the microbiome, revealing distinct microbial communities across various tumor types. These microbes engage in bidirectional interactions with tumor cells and the immune system, shaping the inflammatory milieu and immune responses that ultimately influence tumor outcomes. Consequently, manipulating tumor-associated microbiota has become an exciting strategy to enhance cancer therapy. By harnessing tailored physicochemical properties and structural design, nanotechnology-based drug platforms can precisely remove tumor-associated microbiota and microbial communities within the TME, while simultaneously delivering antimicrobials, immunomodulators, or probiotics to boost immune responses and overcome resistance. However, the complexity and heterogeneity of the microbiome and TME present significant challenges in the development of universal therapeutic approaches. This review highlights the role of tumor-associated microbiota in tumor biology, the mechanisms by which microbiota influence tumor progression and therapeutic resistance, and the potential of nanodrug-based strategies for microbiome modulation in cancer treatment. By elucidating these mechanisms, we aim to provide insights into the therapeutic potential of microbiome-targeted therapies for precision oncology.
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http://dx.doi.org/10.1016/j.jconrel.2025.114196 | DOI Listing |
J Control Release
September 2025
Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, Department of Pharmaceutics, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, PR China. Electronic address:
The tumor microenvironment (TME) is a complex and dynamic ecosystem that significantly influences tumor progression, immune modulation, and therapeutic response. A key component of the TME is the tumor-associated microbiota, which has emerged as an important player in cancer biology, affecting tumor metastasis, immune evasion, and resistance to treatments. The recent advent of high-throughput sequencing technologies has revolutionized our understanding of the microbiome, revealing distinct microbial communities across various tumor types.
View Article and Find Full Text PDFMol Oncol
September 2025
IRCCS Humanitas Research Hospital, Milan, Italy.
The discovery of tumor-associated bacteria (TAB) challenges the traditional view of tumors as sterile environments. These microbes are engaged in a complex dialog with the other components of the tumor microenvironment (TME), influencing immunity, metastasis, and treatment response. Yet the precise mechanisms by which TAB influence tumor biology remains incompletely understood.
View Article and Find Full Text PDFNat Metab
September 2025
Chair of Nutrition and Immunology, School of Life Sciences, Technische Universität München, Freising-Weihenstephan, Munich, Germany.
Endoplasmic reticulum unfolded protein responses contribute to cancer development, with activating transcription factor 6 (ATF6) involved in microbiota-dependent tumorigenesis. Here we show the clinical relevance of ATF6 in individuals with early-onset and late colorectal cancer, and link ATF6 signalling to changes in lipid metabolism and intestinal microbiota. Transcriptional analysis in intestinal epithelial cells of ATF6 transgenic mice (nATF6) identifies bacteria-specific changes in cellular metabolism enriched for fatty acid biosynthesis.
View Article and Find Full Text PDFInt J Mol Sci
August 2025
Anatomic Pathology Unit, Department of Human Pathology in Adult and Developmental Age "Gaetano Barresi", University of Messina, 98125 Messina, Italy.
(), a Gram-negative anaerobe traditionally associated with periodontal disease, has recently emerged as a putative contributor to gastric carcinoma (GC) pathogenesis. Beyond its detection in gastric tissues, particularly in patients negative for () or in advanced GC cases, exerts diverse oncogenic effects. It promotes GC progression by modulating the tumor microenvironment through IL-17/NF-κB signaling, inducing tumor-associated neutrophils (TANs), upregulating PD-L1 expression, and enhancing immune evasion.
View Article and Find Full Text PDFInt Immunopharmacol
August 2025
Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China; Fujian Abdominal Surgery Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China; Department of Hepatobiliary and Pancreatic
Pancreatic ductal adenocarcinoma (PDAC) exhibits a particularly immunosuppressive microenvironment, which contributes to its poor prognosis and resistance to conventional therapies. Recent studies have highlighted the microbiome as a dynamic regulator of anti-tumor immunity, ultimately contributing to tumor suppression. The tumor microenvironment is increasingly recognized as a dynamic ecosystem where the microbiome plays a pivotal role in shaping immune responses.
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