Engineered Microbial Immunotherapies for Cancer: Mechanisms, Translation, and Clinical Potential

Microbial-based cancer immunotherapy represents a rapidly evolving frontier in oncology, integrating advances from cancer genetics, immunology, synthetic biology, and microbiology. Despite recent successes, the effectiveness of immunotherapies against solid tumors remains limited by the complexity of the tumor microenvironment (TME), which is often immunosuppressive, poorly infiltrated by immune cells, and shaped by intricate metabolic and genetic barriers. Current research has revealed that the interplay between tumor genomic alterations, immune evasion mechanisms, and the presence of microbial communities within the TME profoundly influence patient responses to therapy. However, knowledge gaps remain regarding the precise molecular mechanisms by which the microbiome, microbial metabolites, and engineered bacteria interact with and modify host and tumor gene expression, antigen presentation, and immune effector functions. Significant studies now demonstrate that leveraging synthetic biology to design bacteria or harness microbial-derived products can remodel tumor immunity. Yet, a deeper systems-level understanding of these processes, and validated predictive genomic and RNA-based biomarkers, are urgently needed to move the field forward.This Research Topic aims to dissect the genetic, genomic, and molecular bases by which microbial platforms shape and modulate anti-tumor immunity, with a special focus on mechanisms that are traceable through large-scale genomic, transcriptomic, and multi-omic profiling. The objective is to bring together diverse specialists to explore how genetic determinants in both host and tumor define susceptibility or resistance to microbial-based therapies, identify actionable molecular targets, and delineate the pathways by which microbes influence the immune microenvironment. By encouraging cross-disciplinary studies and the development of novel molecular biomarkers, the topic seeks to catalyze a mechanistic understanding that will underpin the next generation of precision microbial immunotherapies.The scope of this Research Topic encompasses mechanistic, translational, and computational studies that illuminate the molecular interplay between microbes and tumor or host genomes, but does not cover unrelated aspects of immunotherapy outside of genomic and molecular investigations. Both hypothesis-driven and exploratory research addressing the genetic and molecular dimensions of microbial-based cancer immunotherapy are welcome. To gather further insights in the genomic and molecular architecture of microbial platforms in cancer, we welcome articles addressing, but not limited to, the following themes:- Genomic and transcriptomic profiling of tumor–microbiome interactions.- Identification and validation of RNA-based and genomic biomarkers predictive of microbial immunotherapy response.- Integration of multi-omics approaches combining microbiome and tumor genomic data.- Elucidation of genetic determinants underlying tumor susceptibility or resistance to microbial therapies.- Mechanistic studies of microbial-derived metabolite regulation of gene expression within the TME.- Bioinformatic and systems biology analyses of microbial–host genomic interactions. - Correlation of microbiome-induced genetic or epigenetic changes with pathology and patient outcomes.- Identification of molecular targets for the clinical translation of microbial therapies.- Translational genomics supporting the development and deployment of microbial-based cancer immunotherapeutics.- Novel molecular rationales for integrating microbial interventions with genomics-guided oncology approaches.Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases that are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of the scope of this Research Topic.Topic Editor Paul de Figueiredo has declared the following conflict of interest: he holds equity in Tranquility Biodesign, LLC, SUHO Biotechnology, LLC, SUBI Biotechnology, ROXO, and HelioWave Technologies, Inc., companies he co-founded. All other Topic Editors declare no competing interests with regards to the Research Topic. Topic editors: Jianxun J. Song, Koichi S Kobayashi, Paul de Figueiredo Source: https://www.frontiersin.org/research-topics/80737/engineered-microbial-immunotherapies-for-cancer-mechanisms-translation-and-clinical-potential