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Science China Life Sciences 2025年第5期68卷 1536-1540页

作者： Hao Xu Shibo Zhou Zefeng Zhu Vincenzo Vitelli Liangyi Chen Ziwei Dai Ning Yang Luhua Lai Shengyong Yang Sergey Ovchinnikov Zhuoran Qiao Sirui Liu Chen Song Jianfeng Pei Han Wen Jianfeng Feng Yaoyao Zhang Zhengwei Xie Yang-Yu Liu Zhiyuan Li Fulai Jin Hao Li Mohammad Lotfollahi Xuegong Zhang Ge Yang Shihua Zhang Ge Gao Pulin Li Qi Liu Jing-Dong Jackie Han Peking-Tsinghua Center for Life Sciences (CLS) Academy for Advanced Interdisciplinary StudiesPeking University Center for Quantitative Biology (CQB) Academy for Advanced Interdisciplinary StudiesPeking University Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program Academy for Advanced Interdisciplinary StudiesPeking University Department of Physics University of Chicago School of Life Sciences Southern University of Science and Technology Peking University Chengdu Academy for Advanced Interdisciplinary Biotechnologies College of Chemistry and Molecular Engineering Peking University Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan University Department of Biology Massachusetts Institute of Technology Lambic Therapeutics Inc. Changping Laboratory Al for Science Institute Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence Fudan University Department of Obstetrics and Gynecology West China Second University HospitalSichuan University Peking University International Cancer Institute and Peking University-Yunnan Baiyao International Medical Institute and State Key Laboratory of Natural and Biomimetic Drugs Department of Molecular and Cellular PharmacologySchool of Pharmaceutical SciencesPeking University Health Science CenterPeking University Channing Division of Network Medicine Department of MedicineBrigham and Women's Hospital and Harvard Medical School Center for Artificial Intelligence and Modeling the Carl R.Woese Institute for Genomic BiologyUniversity of Illinois Urbana-Champaign Department of Genetics and Genome Sciences School of Medicine and Department of Computer and Data Sciences and Department of Population and Quantitative Health SciencesCase Western Reserve University Department of Biochemistry and Biophysics University of California Sanger Institute Department of Automation Tsinghua University State Key Laboratory of Multimodal Artificial Intelligence Systems I

The development of artificial intelligence(AI) and the mining of biomedical data complement each other. From the direct use of computer vision results to analyze medical images for disease screening, to now integrating biological knowledge into models and even accelerating the development of new AI based on biological discoveries, the boundaries of both are constantly expanding, and their connections are becoming closer.

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Author Correction: ChromaFold predicts the 3D contact map from single-cell chromatin accessibility

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Nature communications 2025年第1期16卷 684页

作者： Vianne R Gao Rui Yang Arnav Das Renhe Luo Hanzhi Luo Dylan R McNally Ioannis Karagiannidis Martin A Rivas Zhong-Min Wang Darko Barisic Alireza Karbalayghareh Wilfred Wong Yingqian A Zhan Christopher R Chin William S Noble Jeff A Bilmes Effie Apostolou Michael G Kharas Wendy Béguelin Aaron D Viny Danwei Huangfu Alexander Y Rudensky Ari M Melnick Christina S Leslie Computational and Systems Biology Program Memorial Sloan Kettering Cancer Center New York NY USA. Tri-Institutional Program in Computational Biology and Medicine New York NY USA. University of Washington Seattle WA USA. Developmental Biology Program Sloan Kettering Institute New York NY USA. Molecular Pharmacology Program Experimental Therapeutics Center and Center for Stem Cell Biology Memorial Sloan Kettering Cancer Center New York NY USA. Caryl and Israel Englander Institute for Precision Medicine Institute for Computational Biomedicine Weill Cornell Medicine Cornell University New York NY USA. Division of Hematology and Medical Oncology Department of Medicine Weill Cornell Medical College New York NY USA. Department of Biochemistry & Molecular Biology Sylvester Comprehensive Cancer Center University of Miami Miller School of Medicine Miami FL USA. Howard Hughes Medical Institute and Immunology Program Sloan Kettering Institute and Ludwig Center at Memorial Sloan Kettering Cancer Center New York NY USA. Center for Epigenetics Research Memorial Sloan Kettering Cancer Center New York NY USA. Joan and Sanford I. Weill Department of Medicine Sandra and Edward Meyer Cancer Center Weill Cornell Medicine New York NY USA. Departments of Medicine Division of Hematology & Oncology and of Genetics & Development Columbia Stem Cell Initiative Herbert Irving Comprehensive Cancer Center Columbia University Irving Medical Center New York NY USA. Computational and Systems Biology Program Memorial Sloan Kettering Cancer Center New York NY USA. lesliec@***.

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Results of a Phase 1 Open Label Dose Escalation Trial of AB-205 (Allogeneic Engineered Endothelial Cell Therapy) in Adults with Lymphoma Undergoing High-Dose Therapy and Autologous Hematopoietic Cell Transplantation (HDT-AHCT)

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BLOOD 2020年 136卷 14-15页

作者： Scordo, Michael Budde, Lihua E. Abedi, Mehrdad Mulroney, Carolyn Fakhri, Bita Pawarode, Attaphol Dholaria, Bhagirathbhai Kavalerchik, Edward Aggarwal, Sanjay K. Qazilbash, Muzaffar H. Finnegan, Paul Giralt, Sergio A. Adult Bone Marrow Transplant Service Department of Medicine Memorial Sloan-Kettering Cancer Center/New York New York NY T Cell Therapeutics Research Laboratory Department of Hematology and Hematopoietic Cell Transplantation City of Hope National Medical Center Duarte CA UC Davis Medical Center Sacramento CA UCSD Moores Cancer Center La Jolla CA Division of Hematology and Oncology University of California San Francisco CA Blood and Marrow Transplant Program University of Michigan Ann Arbor MI Department of Medicine Division of Hematology and Oncology Vanderbilt University Medical center Nashville TN Clinical Development Angiocrine Bioscience San Francisco CA Clinical Development Angiocrine Bioscience San Diego CA Department of Stem Cell Transplantation and Cellular Therapy The University of Texas MD Anderson Cancer Center Houston TX Angiocrine Bioscience San Diego CA Department of Medicine Adult Bone Marrow Transplantation Service Memorial Sloan Kettering Cancer Center New York NY Memorial Sloan Kettering Cancer Center New York NY

Introduction: HDT-AHCT is a standard and potentially curative therapy for patients with high risk, chemosensitive lymphomas. Improvements in supportive care and HCT practices have led to increasing use of HDT-AHCT worldwide particularly in elderly and more comorbid patients at higher risk of complications. However, HDT is associated with severe regimen-related toxicities (SRRT) which lead to considerable symptom burden and in some cases, life-threatening organ toxicities. Moreover, the risk of SRRT is a significant concern and may lead to patients being denied a potentially curative therapy. Although SRRT can affect many organs, the most commonly affected are those with high cell turnover, including the hematopoietic system and oral-gastrointestinal tract (oral/GI tract). While the hematopoietic system is rescued by AHCT, there are no effective therapies to substantially reduce SRRT. AB-205 is a novel experimental engineered-cell therapy intended to reduce SRRT associated with HDT-AHCT. AB-205 contains clinical-grade, allogeneic E4ORF1 + CD31 + umbilical vein endothelial cells, or ’universal’ E-CEL® cells, and has been shown to accelerate the recovery of the vascular niches in various organs through autocrine and juxtacrine mechanisms of action on resident tissue capillary endothelial cells and resident progenitors in preclinical studies. It also has a beneficial effect in chaperoning exogenously administered stem cells. Here we report results of a Phase I study of AB-205 in adults with lymphoma undergoing HDT-AHCT. Methods: The primary objective is to assess the safety of AB-205. Secondary objectives include assessment of grade (G) ≥ 3 AEs (NCI-CTCAE v5.0), G ≥ 3 oral/GI SSRT (defined as oral mucositis (OM), nausea, vomiting and diarrhea) and time to neutrophil and platelet engraftment. Subjects with chemosensitive lymphomas who are eligible for HDT-AHCT using myeloablative conditioning regimens were enrolled. Three dose-levels have been tested: 5, 10 and 20 x 10 6

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Growth factors profile in conditioned medium human adipose tissue-derived mesenchymal stem cells (CM-hATMSCs)

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Clinical Nutrition Experimental 2019年 24卷 34-44页

作者： Noverina, Rachmawati Widowati, Wahyu Ayuningtyas, Wireni Kurniawan, Dedy Afifah, Ervi Laksmitawati, Dian Ratih Rinendyaputri, Ratih Rilianawati, Rilianawati Faried, Ahmad Bachtiar, Indra Wirakusumah, Firman Fuad Laboratory Animal and Stem Cells PT Bio Farma (Persero) Bandung 40161 West Java Indonesia Doctoral Program Faculty of Medicine Universitas Padjadjaran Bandung Indonesia Medical Research Center Faculty of Medicine Maranatha Christian University Bandung West Java Indonesia Master Program Faculty of Medicine Universitas Padjadjaran Bandung West Java Indonesia Biomolecular and Biomedical Research Center Aretha Medika Utama Bandung West Java Indonesia Faculty of Pharmacy Pancasila University Jakarta Indonesia National Institute of Health Research and Development Ministry of Health Jakarta Indonesia Agency for the Assessment and Application of Technology Ministry of Research and Technology Serpong Indonesia Department of Neurosurgery and Stem Cell Working Group Faculty of Medicine Universitas Padjadjaran-Dr. Hasan Sadikin Hospital Bandung Indonesia Stem Cell and Cancer Institute PT Kalbe Farma (Tbk.) Jakarta Indonesia Department of Obstetrics and Gynecology Faculty of Medicine Universitas Padjadjaran-Dr. Hasan Sadikin Hospital Bandung Indonesia

Background: stem cell-derived by conditioned medium has potential as regenerative agent of skin cells because it contains many growth factors, cytokines and other regenerative biomolecules. Conditioned medium (CM) from human adipose tissue-derived MSCs (CM-hATMSCs) also has been known enriched growth factors that play an important role in epithelial wound repair, reduce wrinkles, and enhance wound healing. Objective: This study was performed to evaluate growth factors in CM such as Transforming Growth Factor (TGF)-β1, TGF-β2, Vascular Endothelial Growth Factor (VEGF)-2, Vascular Cell Adhesion Molecule (VCAM) 1, Epidermal Growth Factor (EGF), Fibroblast Growth Factor (FGF) in CM-hATMSCs treated with Fresh Frozen Plasma (FFP) and non-FFP at various passages. Methods: This study used ELISA method to measure the growth factors in CM-hATMSCs. Results: FGF was the highest modulator among FFP and non-FFP-treated cells at many passages compared to the others growth factor. Both FFP and non-FFP-treated cells showed significant difference (P < 0.05) in some growth factors. However, there was no significant differences in TGF-β1 at passage 3,7,11 and 15 in FFP-treated cells and non-FFP-treated cells. Conclusion: In summary, the highest concentration level found in CM-hATMSCs is FGF both in FFP and non-FFP-treated cells. FGF as growth factor composition in CM-hATMSCs has potential as wound healing and regeneration of cell and it can be used in anti-aging products. © 2019 The Authors

关键词： Conditioned medium Fresh frozen plasma Growth factor Human adipose tissue derived-mesenchymal stem cells Wound healing

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O-171 Apicobasal RNA asymmetries regulate cell fate in the early mouse embryo

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Human Reproduction 2024年第Supplement_1期39卷

作者： Hawdon, A Geoghegan, N D Mohenska, M Elsenhans, A Ferguson, C Polo, J M Parton, R G Zenker, J Australian Regenerative Medicine Institute ARMI- Monash University & Monash IVF Faculty of Medicine- Nursing and Health Sciences Melbourne Australia Walter and Eliza Hall Institute of Medical Research Department of Medical Biology- University of Melbourne Melbourne Australia Monash Biomedicine Discovery Institute Department of Anatomy and Developmental Biology- Development and Stem Cells Program Melbourne Australia University of Adelaide South Australian immunoGENomics Cancer Institute Adelaide Australia University of Adelaide Adelaide Centre for Epigenetics Adelaide Australia University of Duisburg-Essen Department of Biology Essen Germany University of Queensland Institute for Molecular Bioscience Brisbane Australia University of Queensland Centre for Microscopy and Microanalysis Brisbane Australia

Assessing the morphological appearance of an embryo as it progresses from zygote to blastocyst is the primary method used by embryologists to evaluate embryo viability and developmental potential. Standard embryo grading techniques, using time-lapse microscopy, analyse morphological characteristics such as size, shape, number, and appearance of blastomeres. The aim of this study was to determine how individual cells of the embryo function on a subcellular level to build a healthy *** localisation plays indispensable roles in establishing asymmetries and coordinating cell fate decisions during early embryogenesis across various non-mammalian species. To direct the spatiotemporal distribution of RNA within the cells of an embryo, the microtubule cytoskeleton provides highly sophisticated trafficking pathways. Yet, it remains unknown whether subcellular heterogeneities exist during mammalian preimplantation development and how they contribute to cell fate *** advanced live imaging, we visualised global RNA transcripts at high spatiotemporal resolution from fertilisation to the blastocyst stage in living preimplantation mouse embryos. We discovered apicobasal RNA asymmetries specific to outer cells of the 16-cell stage mouse embryo, coinciding with cell fate decisions and the emergence of the pluripotent inner cell mass. Highly clustered RNAs accumulated proximal to the basal membrane, while more dispersed RNA foci were identified apically as the embryo reaches the late 16-cell stage. The targeted distribution of membrane-less RNA molecules was facilitated by the microtubule cytoskeleton, associated with lysosomes which serve as RNA transport *** discovered that apically located RNA foci were more dynamic and accompanied an enrichment of translation components. Furthermore, we uncovered that the established RNA asymmetries enhanced translation capacity in apical regions compared to basal regions. These spatiotemporal RNA heterogeneities we

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A STAT3 protein complex required for mitochondrial mRNA stability and cancer

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Cell Reports 2023年第9期42卷 113033页

作者： Fernando, C. Dilanka Jayasekara, W. Samantha N. Inampudi, Chaitanya Kohonen-Corish, Maija R.J. Cooper, Wendy A. Beilharz, Traude H. Josephs, Tracy M. Garama, Daniel J. Gough, Daniel J. Department of Molecular Translational Science Faculty of Medicine Nursing and Health Sciences Monash University Clayton 3800 VIC Australia Centre for Cancer Research Hudson Institute of Medical Research Clayton 3168 VIC Australia Garvan Institute of Medical Research Darlinghurst 2010 NSW Australia Woolcock Institute of Medical Research Glebe 2037 NSW Australia School of Medicine Western Sydney University Campbelltown 2560 NSW Australia Faculty of Science UTS Sydney Ultimo 2007 NSW Australia Tissue Pathology and Diagnostic Oncology NSW Health Pathology Royal Prince Alfred Hospital Missenden Road Camperdown 2050 NSW Australia Sydney Medical School University of Sydney Camperdown 2006 NSW Australia Development and Stem Cells Program and the Department of Biochemistry and Molecular Biology Biomedicine Discovery Institute Monash University Clayton 3800 VIC Australia Drug Discovery Biology Theme Monash Institute of Pharmaceutical Sciences Monash University Parkville 3052 VIC Australia ARC Centre for Cryo-Electron Microscopy of Membrane Proteins Monash Institute of Pharmaceutical Sciences Monash University Parkville 3052 VIC Australia

Signal transducer and activator of transcription 3 (STAT3) is a potent transcription factor necessary for life whose activity is corrupted in diverse diseases, including cancer. STAT3 biology was presumed to be entirely dependent on its activity as a transcription factor until the discovery of a mitochondrial pool of STAT3, which is necessary for normal tissue function and tumorigenesis. However, the mechanism of this mitochondrial activity remained elusive. This study uses immunoprecipitation and mass spectrometry to identify a complex containing STAT3, leucine-rich pentatricopeptide repeat containing (LRPPRC), and SRA stem-loop-interacting RNA-binding protein (SLIRP) that is required for the stability of mature mitochondrially encoded mRNAs and transport to the mitochondrial ribosome. Moreover, we show that this complex is enriched in patients with lung adenocarcinoma and that its deletion inhibits the growth of lung cancer in vivo, providing therapeutic opportunities through the specific targeting of the mitochondrial activity of STAT3. © 2023 The Author(s)

关键词： CP: Cancer CP: Molecular biology LRPPRC lung adenocarcinoma mitochondria mRNA stability SLIRP STAT3

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ESMO-Magnitude of Clinical Benefit Scale for haematological malignancies (ESMO-MCBS:H) version 1.0

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Annals of Oncology 2023年第9期34卷 734-771页

作者： Kiesewetter, B. Dafni, U. de Vries, E.G.E. Barriuso, J. Curigliano, G. González-Calle, V. Galotti, M. Gyawali, B. Huntly, B.J.P. Jäger, U. Latino, N.J. Malcovati, L. Oosting, S.F. Ossenkoppele, G. Piccart, M. Raderer, M. Scarfò, L. Trapani, D. Zielinski, C.C. Wester, R. Zygoura, P. Macintyre, E. Cherny, N.I. Division of Oncology Department of Medicine I Medical University of Vienna Vienna Austria Laboratory of Biostatistics School of Health Sciences National and Kapodistrian University of Athens Athens Greece Frontier Science Foundation-Hellas Athens Greece Department of Medical Oncology University Medical Center Groningen University of Groningen Groningen Netherlands The Christie NHS Foundation Trust and Division of Cancer Sciences School of Medical Sciences Faculty of Biology Medicine and Health University of Manchester Manchester United Kingdom European Institute of Oncology IRCCS Division of Early Drug Development Milan Italy Department of Oncology and Hemato-Oncology University of Milano Milan Italy Servicio de Hematología Hospital Universitario de Salamanca-IBSAL CIBERONC and Centro de Investigación del Cáncer-IBMCC (USAL-CSIC) Salamanca Spain ESMO Head Office Lugano Switzerland Departments of Oncology Public Health Sciences Queen's University Kingston Canada Division of Cancer Care and Epidemiology Queen's University Kingston Canada Cambridge Stem Cell Institute Department of Haematology University of Cambridge & Cambridge University Hospitals Cambridge United Kingdom Department of Medicine I Clinical Division of Hematology and Hemostaseology Medical University of Vienna Vienna Austria Department of Molecular Medicine University of Pavia Pavia Italy Department of Hematology Oncology IRCCS S. Matteo Hospital Foundation Pavia Italy Department of Haematology VU University Medical Center Amsterdam Netherlands Institut Jules Bordet Hôpital Universitaire de Bruxelles (HUB) Université Libre de Bruxelles (ULB) Brussels Belgium Strategic Research Program on CLL Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele Milan Italy Wiener Privatklinik Central European Academy Cancer Center Vienna Austria Department of Hematology Erasmus MC Cancer Institute Rotterdam Netherlands Onco-hématologie Biologique AP-HP Necker-Enfants Malades Hospita

Background: The European Society for Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS) has been accepted as a robust tool to evaluate the magnitude of clinical benefit reported in trials for oncological therapies. However, the ESMO-MCBS hitherto has only been validated for solid tumours. With the rapid development of novel therapies for haematological malignancies, we aimed to develop an ESMO-MCBS version that is specifically designed and validated for haematological malignancies. Methods: ESMO and the European Hematology Association (EHA) initiated a collaboration to develop a version for haematological malignancies (ESMO-MCBS:H). The process incorporated five landmarks: field testing of the ESMO-MCBS version 1.1 (v1.1) to identify shortcomings specific to haematological diseases, drafting of the ESMO-MCBS:H forms, peer review and revision of the draft based on re-scoring (resulting in a second draft), assessment of reasonableness of the scores generated, final review and approval by ESMO and EHA including executive boards. Results: Based on the field testing results of 80 haematological trials and extensive review for feasibility and reasonableness, five amendments to ESMO-MCBS were incorporated in the ESMO-MCBS:H addressing the identified shortcomings. These concerned mainly clinical trial endpoints that differ in haematology versus solid oncology and the very indolent nature of nevertheless incurable diseases such as follicular lymphoma, which hampers presentation of mature data. In addition, general changes incorporated in the draft version of the ESMO-MCBS v2 were included, and specific forms for haematological malignancies generated. Here we present the final approved forms of the ESMO-MCBS:H, including instructions. Conclusion: The haematology-specific version ESMO-MCBS:H allows now full applicability of the scale for evaluating the magnitude of clinical benefit derived from clinical studies in haematological malignancies. © 2023

关键词： clinical benefit clinical trials ESMO-MCBS haematological malignancies quality of life value frameworks

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Correction: stem cell transcriptional profiles from mouse subspecies reveal cis-regulatory evolution at translation genes

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Heredity 2024年第5期133卷 370页

作者： Noah M Simon Yujin Kim Joost Gribnau Diana M Bautista James R Dutton Rachel B Brem Biology of Aging Doctoral Program Leonard Davis School of Gerontology University of Southern California Los Angeles CA 90089 USA. Buck Institute for Research on Aging Novato CA 94945 USA. Department of Plant and Microbial Biology University of California Berkeley Berkeley CA 94720 USA. Stem Cell Institute University of Minnesota Minneapolis MN 55455 USA. Department of Genetics Cell Biology and Development University of Minnesota Minneapolis MN 55455 USA. Department of Reproduction and Development Erasmus MC Rotterdam PO Box 2040 CA 3000 Netherlands. Department of Molecular and Cell Biology University of California Berkeley Berkeley CA 94720 USA. Buck Institute for Research on Aging Novato CA 94945 USA. rbrem@berkeley.edu. Department of Plant and Microbial Biology University of California Berkeley Berkeley CA 94720 USA. rbrem@berkeley.edu.

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Cover Image, Volume 236, Number 9, September 2021

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Journal of Cellular Physiology 2021年第9期236卷

作者： Fatemeh Ghaemimanesh Majid Mehravar Saeideh Milani Ensieh M. Poursani Kioomars Saliminejad Monoclonal Antibody Research Center Avicenna Research Institute ACECR Tehran Iran Department of Anatomy and Developmental Biology Development and Stem Cells Program Biomedicine Discovery Institute Monash University Melbourne Australia Blood Transfusion Research Center High Institute for Research and Education in Transfusion Medicine Tehran Iran Hematology Oncology and Stem Cell Transplantation Research Center Tehran University of Medical Sciences Tehran Iran Reproductive Biotechnology Research Center Avicenna Research Institute ACECR Tehran Iran

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Effector Site Immune Dynamics in Refractory Chronic Graft-Versus-Host Disease: A Rockstar Trial Companion Study after Belumosudil Treatment.

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Transplantation and Cellular Therapy 2024年第2期30卷 S269-S270页

作者： Sharma, Rubina, PhD Holtzman, Noa G., MD Pusic, Dr. Iskra, MD, MSCI Cutler, Dr. Corey, MD, MPH, FRCPC Treister, Nathaniel, DMD, DMSc Mehta, Rohtesh S., MD, MPH, MS Alousi, Amin M., MD Vigneswaran, Nadarajah, BDS, DrMedDent, DMD Schueller, Olivier, PhD Macé, Sandrine, PhD Yao, Yu, MD Ji, Ran, PhD Hu, Beifang, PhD Marshall, Kathy Blazar, Bruce R., MD Lee, Stephanie J, MD, MPH Pavletic, Dr. Steven Z., MD, MS Mays, Jacqueline W., DDS, MHSc, PhD National Institute of Dental and Craniofacial Research National Institutes of Health Bethesda MD Immune Deficiency Cellular Therapy Program Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD Medicine Division of Oncology Washington University School of Medicine St. Louis MO Division of Transplantation and Cellular Therapy Department of Medical Oncology Dana-Farber Cancer Institute Boston MA Division of Oral Medicine and Dentistry Brigham and Women's Hospital Boston MA Clinical Research Division Fred Hutchinson Cancer Center Seattle WA Department of Stem Cell Transplantation and Cellular Therapy The University of Texas MD Anderson Cancer Center Houston TX University of Texas School of Dentistry at Houston Houston TX Clinical Development Sanofi Cambridge MA Research and Development Sanofi Chilly-Marzarin France Medical Affairs Sanofi Bridgewater NJ Department of Pediatrics Division of Blood & Marrow Transplant & Cellular Therapy University of Minnesota Minneapolis MN Fred Hutchinson Cancer Center Seattle WA

IntroductionBelumosudil (KD025) is an oral selective rho-associated coiled-coil kinase 2 (ROCK2) inhibitor approved for 3 rd line therapy of chronic graft-versus-host disease (cGVHD). Prior studies demonstrated reduced peripheral blood IL-17 activity and regulatory T cell recovery after ROCK2 inhibition but did not examine responses directly in cGVHD affected tissues. Here, we report tissue-level cGVHD immune dynamics after 6-months of belumosudil treatment in oral mucosa, salivary glands, and skin. MethodsThis companion study is an extension of the pivotal ROCKstar study and evaluated belumosudil 200 mg QD or BID in a total of twenty participants with oral cGVHD (aged 21-77 years) who received 2 to 5 prior lines of systemic therapy. The primary goal of this study was to characterize changes in the local immune cellular profile and IL-17 signaling before and after 6 months of treatment with belumosudil. Enrolled subjects with oral cGVHD consented to additional collection of saliva, peripheral blood and biopsy of the skin, oral mucosa and labial salivary glands at baseline and six months after initiating belumosudil or upon discontinuation of belumosudil if earlier. Matched biospecimens were blinded and analyzed for immune cells and analytes. Comparisons used paired tests at alpha 0.05. ResultsSignificant changes were identified in cGVHD affected tissues after belumosudil treatment. Responders to belumosudil based on overall (N=12) or oral-specific (N=10) NIH response criteria after treatment demonstrated a decrease in oral mucosal collagen type III and I, respectively. In parallel, multiplex immunohistochemistry identified immune cells including CD3 + and CD4 + that significantly decreased in frequency in oral mucosa after treatment in all subjects (Table 1). A decrease in IL-17 + cells was noted in both oral mucosa (N=14 evaluable pairs) and salivary glands (N=11 evaluable pairs) from all subjects. Fewer trends were noted in skin (N=14 evaluable pairs), though lowe

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