{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:44:58Z","timestamp":1791233098761,"version":"4.1.0"},"reference-count":62,"publisher":"American Society for Clinical Investigation","issue":"12","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":55,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"VHA","award":["BX005599"],"award-info":[{"award-number":["BX005599"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,15]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Primary therapy for high-risk bladder cancer (BCa) is repeated instillations of the tuberculosis vaccine Bacillus Calmette-Gu\u00e9rin (BCG). Although BCG reduces the risk of recurrence by more than half, the mechanisms underlying its immune-activating effects remain unknown. Our objective was to investigate how the immune response differs between BCG responders and nonresponders and to compare systemic and local immune responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We performed scRNA-seq of isolated immune cells adjacent to high-risk bladders in BCG responders and nonresponders before and after BCG. We also compared concurrent scRNA-seq profiles of circulating immune cell populations with those of bladder immune cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      We observed an increase in Th17-like Th1 cells in BCG responders, characterized by greater expression of proinflammatory cytokines. By contrast, nonresponders showed increased CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell exhaustion and Treg cells. We found that the primary mechanism driving divergent T cell activity is altered polarization and immunosuppressive signaling with myeloid cells. Using a machine learning\u2013based approach, we identified that Th17-like Th1 cytokines, such as IL-17, IL-21, and IL-26, are predictive of response, which was subsequently validated in a separate BCG-treated BCa cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Together, these findings suggest that dynamic regulation of myeloid\u2013T cell interactions can be critical for outcomes of BCG-treated BCa.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>BX005599 and BX003692 (Veterans Health Administration), HT94252410507 (Department of Defense), R01CA298333 (National Cancer Institute), and Robert H. Lurie Comprehensive Cancer Center H Foundation Core Facility Pilot Project Award.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci200442","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T17:26:36Z","timestamp":1777915596000},"source":"Crossref","is-referenced-by-count":2,"title":["Divergent macrophage-regulated T cell states determine response to Bacillus Calmette-Gu\u00e9rin vaccine in high-risk bladder cancer"],"prefix":"10.1172","volume":"136","author":[{"given":"Ryan J.","family":"Brown","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology and"},{"name":"Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA."},{"name":"Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mairah 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