{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:55:22Z","timestamp":1789152922150,"version":"build-2803163510"},"reference-count":41,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"846","license":[{"start":{"date-parts":[[2027,4,22]],"date-time":"2027-04-22T00:00:00Z","timestamp":1808352000000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/www.science.org\/content\/page\/science-licenses-journal-article-reuse"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["BC23003"],"award-info":[{"award-number":["BC23003"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["2P50CA098131"],"award-info":[{"award-number":["2P50CA098131"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA68485"],"award-info":[{"award-number":["P30CA68485"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["PO1CA210961"],"award-info":[{"award-number":["PO1CA210961"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,4,22]]},"abstract":"<jats:p>Dynamic biomarkers of therapy response are critical for precision oncology but often rely on serial tissue biopsies, which are invasive and not always feasible. In contrast, peripheral blood offers a minimally invasive, dynamic window into the evolving systemic immune landscape. Leveraging this, we performed RNA sequencing on 546 peripheral blood samples from 160 patients with high-risk stage II\/III human epidermal growth factor receptor 2 (HER2)\u2013negative breast cancer treated with either chemotherapy alone or in combination with immunotherapy (chemoimmunotherapy). Our analysis uncovered immune correlates of tumor subtype and treatment response. For example, samples from patients with triple-negative breast cancer exhibited elevated T cell receptor clonality and robust immune activation profiles. Among patients receiving chemoimmunotherapy, early responders demonstrated high baseline T cell receptor diversity, followed by rapid clonal expansion and activation of T cells after just one treatment cycle. We developed a multiparametric peripheral immune biomarker that integrated baseline and early on-treatment features to predict response to pembrolizumab, which was successfully validated in an independent cohort of 59 patients with breast cancer treated with neoadjuvant dostarlimab. These findings reveal the potential of blood-based immune monitoring to predict immunotherapy benefit, offering an accessible tool for tailoring treatment strategies in breast cancer.<\/jats:p>","DOI":"10.1126\/scitranslmed.aec2358","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T17:58:42Z","timestamp":1776880722000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":4,"title":["Peripheral blood transcriptional profiling predicts tumor subtype and neoadjuvant chemoimmunotherapy outcomes in human breast cancer"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5219-8964","authenticated-orcid":true,"given":"Xiaopeng","family":"Sun","sequence":"first","affiliation":[{"name":"Cancer Biology Program Vanderbilt University, Nashville, TN 37232, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6155-4129","authenticated-orcid":true,"given":"Andres A.","family":"Ocampo","sequence":"additional","affiliation":[{"name":"Cancer Biology Program Vanderbilt University, Nashville, TN 37232, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Hanna","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandie C.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Cancer Biology Program Vanderbilt University, Nashville, TN 37232, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0087-5216","authenticated-orcid":true,"given":"Jacey L.","family":"Marshall","sequence":"additional","affiliation":[{"name":"Cancer Biology Program Vanderbilt University, Nashville, TN 37232, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6080-2924","authenticated-orcid":true,"given":"Julia A.","family":"Steele","sequence":"additional","affiliation":[{"name":"Cancer Biology Program Vanderbilt University, Nashville, TN 37232, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4713-8798","authenticated-orcid":true,"given":"Margaret L.","family":"Axelrod","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3340-213X","authenticated-orcid":true,"given":"Elizabeth C.","family":"Wescott","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan R.","family":"Opalenik","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1297-4251","authenticated-orcid":true,"given":"Angela","family":"DeMichele","sequence":"additional","affiliation":[{"name":"University of Pennsylvania, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9202-4568","authenticated-orcid":true,"given":"Laura J.","family":"Esserman","sequence":"additional","affiliation":[{"name":"University of California San Francisco, San Francisco, CA 94115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minetta C.","family":"Liu","sequence":"additional","affiliation":[{"name":"Natera Inc., San Carlos, CA 94070, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5248-0876","authenticated-orcid":true,"given":"Rita","family":"Nanda","sequence":"additional","affiliation":[{"name":"University of Chicago, Chicago, IL 60637, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3676-653X","authenticated-orcid":true,"given":"Denise M.","family":"Wolf","sequence":"additional","affiliation":[{"name":"University of California San Francisco, San Francisco, CA 94115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2076-5177","authenticated-orcid":true,"given":"Lamorna","family":"Brown Swigart","sequence":"additional","affiliation":[{"name":"University of California San Francisco, San Francisco, CA 94115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4502-0035","authenticated-orcid":true,"given":"Gillian L.","family":"Hirst","sequence":"additional","affiliation":[{"name":"University of California San Francisco, San Francisco, CA 94115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9838-8298","authenticated-orcid":true,"given":"Laura J.","family":"van \u2018t Veer","sequence":"additional","affiliation":[{"name":"University of California San Francisco, San Francisco, CA 94115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3752-4006","authenticated-orcid":true,"given":"Yaomin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 37232, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4263-5974","authenticated-orcid":true,"given":"Justin M.","family":"Balko","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1910549"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2019.6650"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31953-X"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.10.011"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.120360"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-0607"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-3200"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10582"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06498-3"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01323-8"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2112651"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz158"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0197-1"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40631-0"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-019-0022-x"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.21037\/tlcr-21-156"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2022.05.005"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12609-019-00334-2"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2023.41.17_suppl.LBA612"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.1061"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41523-022-00486-y"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41523-025-00776-1"},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","unstructured":"J. Zhang Z. Ji K. N. Smith \u201cChapter Twenty-Two - Analysis of TCR \u03b2 CDR3 sequencing data for tracking anti-tumor immunity \u201d in Methods in Enzymology L. Galluzzi N.-P. Rudqvist Eds. (Academic Press 2019) vol. 629 pp. 443\u2013464.","DOI":"10.1016\/bs.mie.2019.08.006"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0266-5"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-24-3283"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2025-012606"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-23-0519"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.07.012"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2019.11.010"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.8798"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdv571"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4466"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-1449"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17414-y"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-020-01235-8"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2019.05.004"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8458"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2023.04.005"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-024-01508-6"},{"key":"e_1_3_2_41_2","unstructured":"J. Oksanen G. L. Simpson F. Guillaume Blanchet R. Kindt P. Legendre P. R. Minchin R.B. O\u2019Hara P. Solymos M. H. H. Stevens E. Szoecs H. Wagner M. Barbour M. Bedward B. Bolker D. Borcard T. Borman G. Carvalho M. Chirico M. De Caceres S. Durand H. B. A. Evangelista R. F. John M. Friendly B. Furneaux G. Hannigan M. O. Hill L. Lahti C. Martino D. M. Glinn M.-H. Ouellette E. R. Cunha T. Smith A. Stier C. J. F. Ter Braak J. Weedon vegan: Community ecology package (2026); 10.32614\/CRAN.package.vegan."},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.aec2358","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.aec2358","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T17:59:03Z","timestamp":1776880743000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.aec2358"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,22]]},"references-count":41,"journal-issue":{"issue":"846","published-print":{"date-parts":[[2026,4,22]]}},"alternative-id":["10.1126\/scitranslmed.aec2358"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.aec2358","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,22]]},"assertion":[{"value":"2025-09-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaec2358"}}