Remodeling the Tumor Milieu: Harnessing the Microbiome in Gynecological Oncology

Gynecological cancers remain a formidable challenge due to therapy resistance and metastasis, driven largely by the dynamic tumor microenvironment (TME). The human microbiome has emerged as a master regulator of this milieu. Site-specific microbial communities, the gut, the cervicovaginal, and even intratumoral microbiomes, directly and systemically influence cancer progression. They remodel the TME by modulating local immune responses, metabolizing drugs, and producing bioactive molecules that can either suppress or promote carcinogenesis. For instance, cervicovaginal dysbiosis is linked to HPV persistence and inflammation, while gut microbiota can determine immunotherapy efficacy. Harnessing this interplay offers a paradigm shift; by targeting these microbial ecosystems through probiotics, prebiotics, or microbiota transplantation, we can potentially reverse immunosuppression and resensitize tumors to therapy, paving the way for novel, personalized interventions in gynecologic oncology.The human microbiome, particularly the gut and reproductive tract microbiomes, has emerged as a pivotal regulator of cancer development, progression, and therapeutic response. This Research Topic aims to explore the dynamic interplay between the microbiome and the tumor TME in gynecological malignancies, including ovarian, endometrial, and cervical cancers. The core problem to be addressed is the critical translational gap between observing the microbiome's association with gynecologic cancers and actively harnessing it to improve patient outcomes. Currently, research has successfully identified correlations between specific microbial patterns (dysbiosis) and cancer incidence, progression, and treatment response. However, the field remains stuck in this observational phase, lacking the mechanistic understanding and targeted strategies needed to intentionally reprogram the hostile TME into a tumor-suppressive state. We seek to compile cutting-edge research that elucidates the mechanisms by which microbial communities influence immune evasion, metastasis, and treatment resistance. The ultimate goal is to highlight novel strategies that harness the microbiome to remodel the TME, thereby enhancing the efficacy of existing therapies and paving the way for new microbiome-based diagnostics and interventions.This Research Topic is dedicated to moving beyond correlative observations and toward functional, translational applications. Our scope explicitly focuses on elucidating the causative mechanisms by which the gut, cervicovaginal, and intratumoral microbiomes directly shape the TME to influence carcinogenesis, metastasis, and therapy response. We seek contributions that address specific themes, including: • the role of microbial metabolites and antigens in reprogramming the tumor immune landscape• the microbiome's impact on resistance to chemotherapy, immunotherapy, and PARP inhibitors• the development of microbial signatures as diagnostic or prognostic biomarkers• and interventional strategies using probiotics, prebiotics, or microbial consortia to re-sensitize tumors and improve outcomes.We welcome Original Research, Reviews, Clinical Trials, and Perspectives that collectively bridge basic science and clinical practice, ultimately paving the way for microbiome-targeting therapeutics in gynecologic oncology.Please note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal. Topic editors: Afza Ahmad, Syed Mohd Danish Rizvi Source: https://www.frontiersin.org/research-topics/78253/remodeling-the-tumor-milieu-harnessing-the-microbiome-in-gynecological-oncology