{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:28:33Z","timestamp":1787059713344,"version":"build-2736575974"},"reference-count":67,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273248, 81874123"],"award-info":[{"award-number":["82273248, 81874123"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSystems"],"published-print":{"date-parts":[[2026,8,18]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Intratumor bacteria (ITB) have emerged as key modulators in various malignancies; however, their role in clear-cell renal cell carcinoma (ccRCC) remains unclear and elusive. In this study, we analyzed seven independent cohorts (comprising one 16S rRNA sequencing and six bulk RNA sequencing data sets) encompassing 517 ccRCC and 65 paired adjacent normal tissues. Following a rigorous decontamination pipeline, we found that neither microbial diversity nor compositional profiles differed significantly between cancerous and adjacent normal tissues. Thirteen specific genera\u2014including\n                      <jats:italic toggle=\"yes\">Streptococcus<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Rothia<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Cutibacterium<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Corynebacterium<\/jats:italic>\n                      \u2014exhibited significant prognostic associations. The microbial risk scores constructed from these genera demonstrated robust performance in prognostic risk stratification and were validated as an independent prognostic factor for both overall survival and progression-free survival, respectively. Host-microbe interaction analysis revealed correlations between these prognostic genera and oncogenic pathways, particularly those involved in immune regulation and metabolism. Notably, culturomics successfully isolated\n                      <jats:italic toggle=\"yes\">Cutibacterium acnes<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">C. acnes<\/jats:italic>\n                      ) from ccRCC tissues, and higher\n                      <jats:italic toggle=\"yes\">C. acnes'<\/jats:italic>\n                      abundance was correlated with a favorable prognosis. Functional assays revealed that\n                      <jats:italic toggle=\"yes\">C. acnes<\/jats:italic>\n                      inhibits tumor growth and suppresses macrophage M2 polarization. Mechanistically,\n                      <jats:italic toggle=\"yes\">C. acnes<\/jats:italic>\n                      and its primary metabolite, propionic acid, attenuate macrophage M2 polarization by activating TNF signaling. Our findings underscore the protective role of\n                      <jats:italic toggle=\"yes\">C. acnes<\/jats:italic>\n                      in the ccRCC microenvironment and highlight its potential as a target for precision immunotherapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      To address previous methodological limitations, we applied rigorous decontamination to multi-omic datasets to isolate and experimentally validate intratumor bacteria colonization in ccRCC. Comparable profiles between tumorous and normal tissues suggest intratumor bacteria generally act as \u201cpassengers.\u201d We successfully constructed robust microbial risk scores predictive of patient survival. Mechanistically,\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      models demonstrated that\n                      <jats:italic toggle=\"yes\">Cutibacterium acnes<\/jats:italic>\n                      and its metabolite, propionic acid, inhibit tumor growth and suppress M2 macrophage polarization via TNF signaling. These findings highlight the protective role of\n                      <jats:italic toggle=\"yes\">Cutibacterium acnes<\/jats:italic>\n                      in the tumor microenvironment, revealing it as a promising target for precision immunotherapy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/msystems.00500-26","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T13:07:55Z","timestamp":1784120875000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["A comprehensive study of intratumor bacteria in clear-cell renal cell carcinoma identifies\n                    <i>Cutibacterium acnes<\/i>\n                    as a protector via suppression of macrophage M2 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