Impact of intra-tumoral microbiome on the efficacy of neoadjuvant immunochemotherapy in patients with locally advanced oral squamous cell carcinoma.

OBJECTIVE: The predictive value of intratumoral microbiota for the efficacy of neoadjuvant immunochemotherapy, as well as the changes in microbiota before and after treatment, has remained largely unexplored. METHODS: We employed 2bRAD sequencing for Microbiome (2bRAD-M) to analyze 42 specimens from patients with locally advanced oral squamous cell carcinoma (OSCC), focusing on trends in intratumoral microbiota changes before and after neoadjuvant immunochemotherapy, and predicting responses to the treatment. RESULTS: (1) There was no significant difference between the MPRbefore group and nMPRbefore group in terms of α diversity and β diversity at baseline, but Ralstoniaₛp. 000620465, Methylobacteriumᵣhodesianum, Methylobacteriumⱼeotgali, RHAL1ₛp. 901457705, Rothiaₛp. 002418375, and RothiaₘucilaginosaA, which were enriched in immune-related signaling pathways, were significantly more abundant in the nMPRbefore group and could predict the efficacy of neoadjuvant immunotherapy (AUC=0. 74). (2) Importantly, both the α and β diversity of intratumoral microbiota significantly decreased after neoadjuvant immunochemotherapy, regardless of whether we compared the MPRbefore group with MPRₐfter group or the nMPRbefore group with nMPRₐfter group. (3) The abundance of Deinococcusgeothermalis was significantly higher in the nMPRₐfter group, while Burkholderiaᵥietnamiensis was enriched in the MPRₐfter group. These differential microbial populations between the nMPRₐfter group and MPRₐfter group were enriched in metabolism-related pathways such as carbon fixation in photosynthetic organisms, taurine and hypotaurine metabolism, and genetic information processing pathways, including homologous recombination and DNA replication. CONCLUSION: Neoadjuvant immunochemotherapy markedly alters intratumoral microbiota diversity. Baseline and post-treatment microbiota differences between MPR and nMPR groups implicate specific signaling pathways that may influence treatment efficacy in locally advanced OSCC.