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Here, we investigated relationships among CD8\n                    <jats:sup>+<\/jats:sup>\n                    tumor-infiltrating lymphocytes (TILs), the breast tumor microbiome, and tumor metabolome. In a cohort of 46 breast cancer patients,\n                    <jats:italic>Staphylococcus<\/jats:italic>\n                    was the only bacterial genus whose intratumoral abundance positively correlated with cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell markers and innate-like T cell signatures, including multiple KLR-family receptors. Several metabolites were significantly associated with CD8\n                    <jats:sup>+<\/jats:sup>\n                    TILs, among which NADH, \u03b3-glutamyltryptophan, and \u03b3-glutamylglutamate differed between\n                    <jats:italic>Staphylococcus<\/jats:italic>\n                    -positive and\n                    <jats:italic>Staphylococcus<\/jats:italic>\n                    -negative tumors. Analysis of an independent cohort of 314 treatment-na\u00efve patients further showed that the association between intratumoral\n                    <jats:italic>Staphylococcus<\/jats:italic>\n                    , heightened CD8\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    depleted intratumoral NAD metabolites and suppressed tumor growth by activating CD8\n                    <jats:sup>+<\/jats:sup>\n                    TILs. Together, these findings identify a link between low-biomass intratumoral bacteria and local anti-tumor immunity, and highlight\n                    <jats:italic>Staphylococcus<\/jats:italic>\n                    and TIL-associated metabolites as potential biomarkers and therapeutic targets for breast cancer immunotherapy.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-48719-5","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T04:06:53Z","timestamp":1776312413000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Breast tumor microbiome regulates anti-tumor immunity and T cell-associated metabolites"],"prefix":"10.1038","volume":"16","author":[{"given":"Chin-Chih","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Grencewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthik","family":"Chakravarthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Liepold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn M.","family":"Marcho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naseer","family":"Sangwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Tzeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Hoyd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachin R.","family":"Jhawar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen R.","family":"Grobmyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahraa","family":"Al-Hilli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"Sciallis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Spakowicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charis","family":"Eng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"48719_CR1","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1038\/s41572-019-0111-2","volume":"5","author":"N Harbeck","year":"2019","unstructured":"Harbeck, N. et al. 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