乳腺肿瘤微生物组调控抗肿瘤免疫与 T 细胞相关代谢物

The breast tumor microbiome has emerged as a potential regulator of tumor immunity, yet its interactions with intratumoral lymphocytes and metabolites remain poorly defined.

Here, we investigated relationships among CD8+ tumor-infiltrating lymphocytes (TILs), the breast tumor microbiome, and tumor metabolome. In a cohort of 46 breast cancer patients, Staphylococcus was the only bacterial genus whose intratumoral abundance positively correlated with cytotoxic CD8+ T cell markers and innate-like T cell signatures, including multiple KLR-family receptors. Several metabolites were significantly associated with CD8+ TILs, among which NADH, -glutamyltryptophan, and -glutamylglutamate differed between Staphylococcus-positive and Staphylococcus-negative tumors.

Analysis of an independent cohort of 314 treatment-na ve patients further showed that the association between intratumoral Staphylococcus, heightened CD8+ T cell activity, and the KLR-associated innate-like T cell program was specific to triple-negative breast cancer (TNBC). In TNBC mouse models, direct intratumoral injection of Staphylococcus aureus depleted intratumoral NAD metabolites and suppressed tumor growth by activating CD8+ TILs.

Together, these findings identify a link between low-biomass intratumoral bacteria and local anti-tumor immunity, and highlight Staphylococcus and TIL-associated metabolites as potential biomarkers and therapeutic targets for breast cancer immunotherapy.