Microbial and metabolic remodeling of the tumor microenvironment in solid cancer immunotherapy resistance

The tumor microenvironment (TME) comprises diverse cellular and non-cellular components, including stromal cells, fibroblasts, endothelial cells, lymphocytes, myeloid cells, extracellular matrix, metabolites, and microorganisms. Through continuous interactions with tumor cells, these components establish a tumor-supportive niche that contributes to tumor initiation, progression, metastasis, immune evasion, and therapeutic resistance. Increasing evidence indicates that microbial communities, pathogenic infections, and metabolic alterations can reshape the immune composition and functional state of the TME, thereby influencing antigen presentation, T-cell activity, myeloid-cell polarization, inflammatory signaling, and responses to immunotherapy. Although recent studies have identified important links between the microbiota, metabolites, and cancer immunity, the mechanisms connecting these factors to immunotherapy resistance remain incompletely understood. Integrated investigation of tumor–microbe–immune interactions is therefore needed to identify reliable biomarkers and mechanism-based therapeutic strategies. This Research Topic aims to investigate how microbial and metabolic factors remodel the TME and promote resistance to immunotherapy in gastrointestinal and related pathogen-associated solid tumors. It will particularly consider gastric, colorectal, and pancreatic cancers, as well as relevant contexts involving intestinal microbiota, Helicobacter pylori, Epstein–Barr virus, and hepatitis B virus. We welcome studies addressing how pathogens, microbial communities, and metabolites influence tumor cells, immune cells, stromal cells, and therapeutic responses. The Research Topic will also examine whether microbial or metabolic signatures can predict treatment response and how the TME can be therapeutically reprogrammed to restore antitumor immunity. Emphasis will be placed on mechanistic, translational, and experimentally validated research that advances the development of strategies to overcome immunotherapy resistance.The Research Topic will focus on mechanistic and translational studies of microbe- and metabolite-driven TME remodeling in gastrointestinal and pathogen-associated cancers. We welcome original research, reviews, and methods articles addressing, but not limited to, the following themes:• Molecular mechanisms of tumor–TME interactions, including epigenetic, transcriptional, metabolic, and post-transcriptional regulation.• Effects of intestinal microbiota, H. pylori, Epstein–Barr virus, hepatitis B virus, and microbial metabolites on tumor immunity.• Microbial and metabolic regulation of T cells, myeloid cells, macrophages, dendritic cells, fibroblasts, and endothelial cells.• Multi-omics, bioinformatics, epidemiological, and biomarker studies investigating tumor–microbe–immune interactions.• Mechanisms of primary and acquired resistance to immune checkpoint blockade and other immunotherapies.• Microbiota-, metabolite-, immune-, and TME-targeted strategies to restore antitumor immunity and improve therapeutic responses.• Experimental and clinical approaches for validating candidate biomarkers and therapeutic targets.Please note: Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic. Topic editors: Xi Cheng, Zhengyang Yang, Yini Zhu Source: https://www.frontiersin.org/research-topics/84828/microbial-and-metabolic-remodeling-of-the-tumor-microenvironment-in-solid-cancer-immunotherapy-resistance