Academic Journal
Cellular reprogramming during anti-PD-1 and chemotherapy treatment in early-stage primary hormone receptor-positive breast cancer.
| Τίτλος: | Cellular reprogramming during anti-PD-1 and chemotherapy treatment in early-stage primary hormone receptor-positive breast cancer. |
|---|---|
| Συγγραφείς: | Fu J; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Waks AG; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Pimenta E; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Titchen B; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Harvard Division of Medical Sciences PhD Program in Biological and Biomedical Sciences, Harvard University, Cambridge, MA, USA., Bi K; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Camp S; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Pappa T; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Keenan T; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Shannon E; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Vigneau S; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Bemus M; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Nag A; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Thorner AR; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Park J; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., DiLullo M; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA., Wrabel E; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA., Jeselsohn R; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Mittendorf EA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.; Division of Breast Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA., Abravanel DL; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Tolaney SM; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Van Allen EM; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. eliezerm_vanallen@dfci.harvard.edu.; Harvard Medical School, Boston, MA, USA. eliezerm_vanallen@dfci.harvard.edu.; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA. eliezerm_vanallen@dfci.harvard.edu.; Parker Institute for Cancer Immunotherapy, Dana-Farber Cancer Institute, Boston, MA, USA. eliezerm_vanallen@dfci.harvard.edu. |
| Πηγή: | Nature communications [Nat Commun] 2025 Nov 28; Vol. 16 (1), pp. 10704. Date of Electronic Publication: 2025 Nov 28. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : Nature Pub. Group |
| Ιατρικοί όροι (MeSH): | Breast Neoplasms*/drug therapy , Breast Neoplasms*/genetics , Breast Neoplasms*/pathology , Breast Neoplasms*/metabolism , Breast Neoplasms*/immunology , Cellular Reprogramming*/drug effects , Cellular Reprogramming*/genetics , Programmed Cell Death 1 Receptor*/antagonists & inhibitors , Immune Checkpoint Inhibitors*/therapeutic use , Immune Checkpoint Inhibitors*/pharmacology , Antineoplastic Combined Chemotherapy Protocols*/therapeutic use, Tumor Microenvironment/drug effects ; Tumor Microenvironment/immunology ; Paclitaxel/therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; Receptors, Estrogen/metabolism ; Macrophages/immunology ; Macrophages/drug effects ; Receptors, Progesterone/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; T-Lymphocytes/immunology ; Humans ; Female ; Neoadjuvant Therapy ; Middle Aged ; Albumins |
| Περίληψη: | The efficacy of immune checkpoint inhibitors combined with chemotherapy varies among breast cancer subtypes and is particularly less effective in hormone receptor-positive (HR + ) breast cancers. Here, we analyze pre-, on-, and post-treatment biopsies from 20 female patients with stage II-III HR+ breast cancer who participated in a clinical trial of neoadjuvant chemo-immunotherapy with nab-paclitaxel and pembrolizumab. Through single-nucleus RNA and ATAC sequencing of these tumor biopsies, we identified gene expression metaprograms (MPs) associated with differential therapy responses. Here we show that favorable responders exhibit increased activity in pathways related to tumor state transition, T cell effector functions, and pro-inflammatory macrophage states. Unfavorable responders demonstrate increased tumor estrogen signaling and immunosuppressive tumor-immune interactions. In this work, we highlight the interplay between tumor and microenvironmental cells in treatment naïve and exposed HR+ breast cancers and reveal that pivotal shifts in tumor cell, macrophage, and T cell states may mediate response to chemo-immunotherapy. (© 2025. The Author(s).) |
| Competing Interests: | Competing interests: AGW reports consulting or advisory roles for AstraZeneca and AMBRX; speaker’s honoraria from AstraZeneca; and research support (to institution) from Genentech, Gilead, Macrogenics, and Merck. RJ reports consulting or advisory roles for Eli Lilly, AstraZeneca, Pfizer, Novartis, Carrick Therapeutics, GE Health, and Luminex; and research funding from Pfizer, Eli Lilly, and Novartis. EAM reports compensated service on scientific advisory boards for AstraZeneca, BioNTech, and Merck; uncompensated service on steering committees for Bristol Myers Squibb and Roche/Genentech; speakers' honoraria and travel support from Merck Sharp & Dohme; and institutional research support from Roche/Genentech (via SU2C grant) and Gilead. EAM also reports research funding from Susan Komen for the Cure, for which she serves as a Scientific Advisor, and uncompensated participation as a member of the American Society of Clinical Oncology Board of Directors. SMT reports consulting or advisory roles for Novartis, Pfizer/SeaGen, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Bristol Myers Squibb/Systimmune, Daiichi Sankyo, Gilead, Blueprint Medicines, Reveal Genomics, Sumitovant Biopharma, Artios Pharma, Menarini/Stemline, Aadi Bio, Bayer, Jazz Pharmaceuticals, Natera, Tango Therapeutics, eFFECTOR, Hengrui USA, Cullinan Oncology, Circle Pharma, Arvinas, BioNTech, Launch Therapeutics, Zuellig Pharma, Johnson&Johnson/Ambrx, Bicycle Therapeutics, BeiGene Therapeutics, Mersana, Summit Therapeutics, Avenzo Therapeutics, Aktis Oncology, Celcuity, Boehringer Ingelheim, Samsung Bioepis, Olema Pharmaceuticals, Tempus, and Boundless Bio; research funding from Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Bristol Myers Squibb, AstraZeneca, NanoString Technologies, Gilead, SeaGen, OncoPep, Daiichi Sankyo, Menarini/Stemline, Jazz Pharmaceuticals, and Olema Pharmaceuticals; and travel support from Lilly, Gilead, Jazz Pharmaceuticals, Pfizer, Arvinas, and Roche. EMVA reports advisory or consulting roles for Enara Bio, Manifold Bio, Monte Rosa, Novartis Institute for Biomedical Research, Serinus Bio, and TracerDx; research funding from Novartis, BMS, Sanofi, and NextPoint; equity in Tango Therapeutics, Genome Medical, Genomic Life, Enara Bio, Manifold Bio, Microsoft, Monte Rosa, Riva Therapeutics, Serinus Bio, Syapse, TracerDx; institutional patents filed on chromatin mutations and immunotherapy response, and methods for clinical interpretation; and intermittent legal consulting on patents for Foley Hoag Editorial Boards: Science Advances. TEK reports becoming an employee at Merck, after her contributions to this manuscript. The remaining authors declare no competing interests. |
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| Grant Information: | R50 CA265182 United States CA NCI NIH HHS; T32 CA009172 United States CA NCI NIH HHS; SAC21204 Susan G. Komen (Susan G. Komen Breast Cancer Foundation) |
| Substance Nomenclature: | P88XT4IS4D (Paclitaxel) DPT0O3T46P (pembrolizumab) 0 (Antibodies, Monoclonal, Humanized) 0 (Receptors, Estrogen) 0 (Programmed Cell Death 1 Receptor) 0 (Immune Checkpoint Inhibitors) 0 (130-nm albumin-bound paclitaxel) 0 (Receptors, Progesterone) 0 (PDCD1 protein, human) 0 (Albumins) |
| Entry Date(s): | Date Created: 20251129 Date Completed: 20251129 Latest Revision: 20260429 |
| Update Code: | 20260429 |
| PubMed Central ID: | PMC12663104 |
| DOI: | 10.1038/s41467-025-66659-y |
| PMID: | 41315371 |
| Βάση Δεδομένων: | MEDLINE |
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