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<p>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<sup>+</sup> tumor-infiltrating lymphocytes (TILs), the breast tumor microbiome, and tumor metabolome. In a cohort of 46 breast cancer patients, <i>Staphylococcus</i> was the only bacterial genus whose intratumoral abundance positively correlated with cytotoxic CD8<sup>+</sup> T cell markers and innate-like T cell signatures, including multiple KLR-family receptors. Several metabolites were significantly associated with CD8<sup>+</sup> TILs, among which NADH, γ-glutamyltryptophan, and γ-glutamylglutamate differed between <i>Staphylococcus</i>-positive and <i>Staphylococcus</i>-negative tumors. Analysis of an independent cohort of 314 treatment-naïve patients further showed that the association between intratumoral <i>Staphylococcus</i>, heightened CD8<sup>+</sup> 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 <i>Staphylococcus aureus</i> depleted intratumoral NAD metabolites and suppressed tumor growth by activating CD8<sup>+</sup> TILs. Together, these findings identify a link between low-biomass intratumoral bacteria and local anti-tumor immunity, and highlight <i>Staphylococcus</i> and TIL-associated metabolites as potential biomarkers and therapeutic targets for breast cancer immunotherapy.</p>

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Breast tumor microbiome regulates anti-tumor immunity and T cell-associated metabolites

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月16日

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  • Chin-Chih Liu,
  • Dennis Grencewicz,
  • Karthik Chakravarthy,
  • Lin Li,
  • Ruth Liepold,
  • Matthew Wolf,
  • Lynn M. Marcho,
  • Naseer Sangwan,
  • Alice Tzeng,
  • Rebecca Hoyd,
  • Sachin R. Jhawar,
  • Stephen R. Grobmyer,
  • Zahraa Al-Hilli,
  • Andrew P. Sciallis,
  • Daniel Spakowicz,
  • Ying Ni,
  • Charis Eng

摘要

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, γ-glutamyltryptophan, and γ-glutamylglutamate differed between Staphylococcus-positive and Staphylococcus-negative tumors. Analysis of an independent cohort of 314 treatment-naïve 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.