Intratumoral microbiome: the double-edged sword in remodeling cancer immunotherapy

Emerging evidence reveals that intratumoral microbial (ITM) communities within the tumor immune microenvironment (TIME) critically influence tumor progression and immunotherapy response. Studies have shown that resident bacteria within tumors, such as Sphingobacterium multivorum, regulate the secretion of chemokines like CCL20 and CXCL8, promoting the infiltration of regulatory T cells (Tregs) and inhibiting the function of cytotoxic T cells (CD8⁺ T cells)-thereby weakening the efficacy of immune checkpoint inhibitors. Additionally, microbial metabolites may serve as potential biomarkers for predicting sensitivity to immunotherapy. Concurrently, engineered bacteria (e.g., oncolytic mineralizing bacteria) demonstrate significant antitumor effects by activating innate immunity and enhancing antitumor-specific immune responses, providing new strategies to overcome immunotherapy resistance. These findings highlight the dual role of ITM in tumor immune evasion and immunotherapy sensitivity, laying an important theoretical foundation for developing novel immunotherapy strategies targeting tumoral microbiota metabolism.