Immune 105: Tumor bacteria undermine immunotherapy

Epstein-Barr virus (EBV) infection and the HLA-DR15 haplotype synergistically increase multiple sclerosis risk by altering the immunopeptidome of B cells. EBV infection triggers the presentation of myelin basic protein (MBP) peptides on HLA-DR15 molecules, activating autoreactive CD4+ T cells that subsequently infiltrate the central nervous system. Separately, high intratumoral bacterial burden in head and neck squamous cell carcinoma correlates with poor responses to immune checkpoint blockade. These bacterial communities, often dominated by species like *Fusobacterium*, promote an immunosuppressive microenvironment characterized by increased neutrophil recruitment, which hinders the efficacy of PD-1/PD-L1 inhibitors. While antibiotic intervention shows promise in reducing bacterial load and improving anti-tumor immunity in specific models, the systemic impact on the microbiome necessitates cautious clinical application. These findings underscore the complex interplay between microbial presence, immune regulation, and therapeutic resistance in both autoimmune and oncological diseases.