_1698905393 20231102060953000 Rovedar Daryoushbabazadeh@gmail.com Rovedar Journal of Lab Animal Research J Lab Anim. Res 2980-9703 10 25 2023 2 5 Seyed Alireza Taheri https://orcid.org/0009-0005-0798-6946 Mahsa Norouzi https://orcid.org/0009-0003-7325-9646 Atefehsadat Monirvaghefi https://orcid.org/0000-0002-1681-6368 Fatemeh Najafi https://orcid.org/0009-0000-8524-9873 Abdolmahdi Asfaram Meshkinshahr https://orcid.org/0009-0002-4803-5977 Sara Aghili https://orcid.org/0009-0001-2819-739X Golnaz Behzad https://orcid.org/0000-0002-4911-9155 Dorsa Mousavi Khatibi https://orcid.org/0009-0000-1927-9804 Bahare Kasaei https://orcid.org/0009-0003-2531-0902 Armin Batmani https://orcid.org/0009-0003-2773-6704 Introduction: Salmonella typhimurium (S. typhimurium) has emerged as a promising agent for cancer therapy. This systematic review aims to comprehensively analyze the existing literature regarding the utilization of S. typhimurium as a therapeutic strategy against cancer. The present systematic review aimed to evaluate the current state of knowledge regarding the anti-tumor properties of S. typhimurium, encompassing its tumor-targeting mechanisms, impact on tumor growth, modulation of the tumor microenvironment, and potential for combination therapies. Materials and methods: A systematic literature search was conducted across major scientific databases, including PubMed, Web of Science, and Scopus, using predefined search terms. Studies published between 2000 and 2023 were included if they investigated the anti-tumor effects of S. typhimurium in vivo. Studies were independently screened, selected, and evaluated for quality by two reviewers. Results: The systematic review identified 152 relevant studies that met the inclusion criteria. These studies collectively demonstrated the ability of S. typhimurium to selectively target and colonize tumors, resulting in significant tumor growth inhibition in various cancer types. Mechanistic insights revealed that S. typhimurium can induce direct cytotoxicity, modulate the tumor microenvironment, and activate anti-tumor immune responses. Additionally, studies highlighted the potential of combining S. typhimurium with conventional therapies or immune checkpoint inhibitors to enhance therapeutic efficacy. Conclusion: This systematic review underscores the promising potential of S. typhimurium as a novel and multifaceted approach to cancer therapy. The accumulated evidence suggests that S. Typhimurium possesses inherent tumor-targeting capabilities, exerts direct anti-tumor effects, and can synergize with other treatment modalities. 10 25 2023 51 62 https://creativecommons.org/licenses/by/4.0 10.58803/jlar.v2i5.30 https://jlar.rovedar.com/index.php/JLAR/article/view/30 https://jlar.rovedar.com/index.php/JLAR/article/download/30/57 https://jlar.rovedar.com/index.php/JLAR/article/download/30/57 Aganja RP, Sivasankar C, Senevirathne A and Lee JH. 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