Journal Article

Bacteria-based immunosuppressive tumor microenvironment reprogramming: a promising dawn in cancer therapy

Imani Fooladi, Abbas Ali, Abedi, Azam, Akbariqomi, Mostafa, Kheirandish Zarandi, Peyman, Moosazadeh Moghaddam, Mehrdad

2025

Overview

Traditional chemotherapy, a prevalent cancer treatment modality, is associated with significant side effects and often leads to treatment failure. Non-specific drug distribution and chemoresistance are the main factors contributing to this failure. Certain distinctive characteristics of the tumor microenvironment (TME), including hypoxia, acidic pH, and increased interstitial fluid pressure, render cancer cells resistant to conventional treatments. Multiple approaches have been devised to enhance the treatment efficiency of neoplasms and overcome chemoresistance. Nowadays, bacteria-based cancer therapy has garnered significant interest in both preclinical and clinical research, owing to its distinctive mechanism and various applications in eliciting host antitumor immunity. Due to their inherent tumor tropism, elevated motility, and capacity for quick colonization in the conducive TME, bacteria are increasingly being considered for targeted tumor treatment. Bacteria, rich in pathogen-associated molecular patterns (PAMPs), can efficiently stimulate immune cells even inside the immunosuppressive TME, boosting the particular immune detection and eradication of tumor cells. Furthermore, outer membrane vesicles (OMVs), cytoplasmic membrane vesicles (CMVs), and their derived physiological components exhibit analogous functionalities to their parental cells. This review article is representative of the latest innovations in bacteria-based immunosuppressive TME reprogramming. Additionally, the article discusses future directions in this research area, drawing on current advances. Graphical abstract Highlights Salmonella enhances the activity of CTLs and NK cells while reducing Tregs populations within the TME, thereby promoting antitumor immune responses. Listeria infects suppressive myeloid cells, boosting IL-12 and antitumor immunity. Engineered bacteria selectively colonize tumors and deliver immunostimulatory agents, reprogramming the TME to enhance antitumor immunity. Engineered OMVs act as targeted nanocarriers, accumulating in tumors and activating immune responses through PAMP delivery. Bacteria-based therapy exploits tumor hypoxia, overcoming chemo- and radio resistance.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: 19th century / 20th century / Animals / Antigen presentation / Antitumor activity / Apoptosis / Applied Microbiology / Bacteria / Bacteria - immunology / Bacteria - metabolism / Bacteria-based cancer therapy / Bioengineering bacteria / Biological products / Biotechnology / Cancer / Cancer therapies / Care and treatment / Chemistry / Chemistry and Materials Science / Chemoresistance / Chemotherapy / Cytokines / Cytoplasmic membranes / Cytotoxicity / Enzymology / Fluid pressure / Genetic Engineering / Gram-negative bacteria / Gram-positive bacteria / Health aspects / Humans / Hypoxia / Immune response / Immune system / Immunity / Immunostimulation / Immunotherapy / Listeria / Membrane vesicles / Membranes / Methods / Microbial Genetics and Genomics / Microbiology / Microorganisms / Migration / Myeloid cells / Neoplasms / Neoplasms - immunology / Neoplasms - therapy / Neutrophils / Pathogen-Associated Molecular Pattern Molecules / Patients / Radiation therapy / Review / Salmonella / Side effects / Tropism / Tumor cells / Tumor microenvironment / Tumor Microenvironment - immunology / Tumor necrosis factor-TNF / Tumors / Vesicles