Intratumoral Microbiota as Modulators of Cancer Immunity, Therapy Response, and Emerging Therapeutic Delivery Strategies

Intratumoral microbiota—bacteria, fungi, and viruses residing within tumor tissue—are increasingly recognized as active participants in the tumor microenvironment rather than incidental bystanders. Across cancer types, these microbes can shape local inflammation, antigen presentation, and immune cell recruitment, influencing whether tumors become immunologically “hot” or “cold.” They may also remodel tumor metabolism and stress pathways, with downstream effects on immune evasion and responsiveness to immune checkpoint blockade, chemotherapy, radiotherapy, and targeted agents. Yet, the field faces major challenges: low-biomass sampling, contamination control, spatial heterogeneity, and the need to distinguish viable intratumoral communities from translocated microbial components.This Research Topic will bring together mechanistic, translational, and methodological studies that clarify how intratumoral microbes modulate anti-tumor immunity and treatment outcomes, and how they can be leveraged therapeutically. We welcome work spanning spatial multi-omics, imaging and culture-based validation, functional models, and clinically annotated cohorts that link intratumoral microbiota signatures to prognosis and therapy response. Particular emphasis will be placed on emerging strategies that harness or engineer microbes for precision drug delivery—such as bacterial vectors, microbial-derived vesicles, and biomaterial-enabled targeting—while addressing safety, manufacturability, and regulatory considerations. By integrating microbial ecology with tumor immunology and therapeutic innovation, this Topic aims to define actionable pathways for biomarker development and next-generation, microbiome-informed cancer interventions.We welcome articles addressing, but not limited to, the following themes:-Define the ecology and spatial organization of intratumoral microbiota across cancer types and stages-Standardize low-biomass sampling, decontamination controls, and reporting guidelines for intratumoral microbiome studies-Dissect mechanisms linking intratumoral microbes to antigen presentation, T cell priming, and myeloid cell polarization-Clarify microbial impacts on immune checkpoint blockade response and resistance (e.g., PD-1/PD-L1, CTLA-4)-Evaluate how intratumoral microbiota modulate chemotherapy and radiotherapy efficacy and toxicity-Identify microbial metabolites and virulence-associated factors that reprogram tumor and immune metabolism-Link intratumoral microbial signatures with clinical outcomes using well-annotated patient cohorts and prospective validation-Develop imaging, spatial transcriptomics, and multi-omics approaches to localize viable microbes and host responses in situ-Explore engineered bacteria, phage, and microbial extracellular vesicles as targeted therapeutic delivery platforms-Address translational barriers: biosafety, biocontainment, manufacturing, and regulatory pathways for microbe-enabled cancer therapies Topic editors: Satveer Jagwani, Aayushi Laliwala Source: https://www.frontiersin.org/research-topics/79141/intratumoral-microbiota-as-modulators-of-cancer-immunity-therapy-response-and-emerging-therapeutic-delivery-strategies