Intratumoral Bacillus cereus orchestrates stem-like lymphoid niches to potentiate immunotherapy response in hepatocellular carcinoma.

Intratumoral Bacillus cereus promotes stem-like lymphoid niches that enhance PD-1/PD-L1 blockade response in hepatocellular carcinoma.

• Why it matters: HCC shows variable immunotherapy outcomes due to heterogeneity in tertiary lymphoid structures, and identifying predictive immune niches is crucial for improving treatment efficacy.
• What they did: Using spatial multi-omics analysis, the study identified stem-like lymphoid niches (SLNs) characterized by CD70+ ILC2s and progenitor exhausted T cells, which correlate with stronger immunotherapy responses; intratumoral B. cereus promotes SLN accumulation through endothelial IL-33 release and epigenetic activation of lymphoid-organizing genes, with PI-PLC as the bacterial effector.
• The result: Combining PI-PLC with αPD-L1 enhances antitumor immunity, suggesting SLNs as a promising target to boost immunotherapy effectiveness in HCC.