Intratumor microbiota in thyroid cancer: emerging insights into tumorigenesis and therapeutic potential

Abstract

Thyroid cancer incidence has risen sharply in recent decades, yet the mechanisms underlying tumor development and progression remain incompletely understood. Recent evidence reveals that tumors, including thyroid malignancies, harbor distinct microbial communities, termed intratumor microbiota, which may actively influence cancer biology. These microbes can modulate the tumor microenvironment (TME), promote DNA damage, alter oncogenic signaling pathways, and reshape immune responses. In thyroid cancer, papillary thyroid carcinoma (PTC) has been the primary focus, with studies identifying differential microbial composition across histological subtypes, disease stages, and patient sex. Microbial metabolites, genotoxins, and interactions with immune and endocrine pathways may contribute to tumor initiation, progression, and immune evasion. Despite compelling associations, causative mechanisms remain largely unexplored, and technical challenges including low microbial biomass and contamination limit current findings. Advanced sequencing approaches, single-cell and spatial transcriptomics, and functional studies in thyroid cancer models are needed to clarify the role of intratumor microbiota. Understanding these microbial interactions holds promise for novel diagnostics, prognostic biomarkers, and microbiota-targeted therapies, potentially improving personalized treatment strategies for thyroid malignancies.