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

作者：Chupeng Hu, Wenhua You, Yedi Huang, Yuhan Zhang, Jingying Lu, Jianzhou Yuan, Ruimin Shan, Songmao Li, Ran Li, Qing Li, Minghao Li, Yongqiang Gao, Gao-Jun Teng, Yun Chen · 发表于：Cancer Cell · 年份：2026 · DOI：10.1016/j.ccell.2026.07.016 · 研究领域：IL-33, ST2, and ILC Pathways、Immune cells in cancer、Cancer Immunotherapy and Biomarkers

Tertiary lymphoid structures (TLSs) drive antitumor immunity, but their functional heterogeneity translates into inconsistent immunotherapy responses in hepatocellular carcinoma (HCC), raising the question of which immune niches actually predict efficacy. Using spatial multi-omics analysis, we uncover a distinct niche, the stem-like lymphoid niches (SLNs), that correlates with stronger responses to PD-1/PD-L1 blockade. Unlike conventional TLS, SLNs feature a specialized niche of CD70 + type 2 innate lymphoid cells (ILC2s) and progenitor exhausted T (T pex ) cells. Intriguingly, intratumoral Bacillus cereus promotes SLN accumulation via triggering endothelial IL-33 release, which rewires ILC2s metabolism and enhances H3K4me3-mediated epigenetic activation of CD70 , Lta , and Ltb genes, reinforcing the niche’s lymphoid-organizing function. We identify the bacterial phosphoinositide-specific phospholipase C (PI-PLC) as the effector behind this endothelial IL-33 release. Combining PI-PLC with αPD-L1 synergistically amplifies antitumor immunity, highlighting SLNs as a promising target for boosting immunotherapy in HCC.