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Article ; Online: Novel Approaches to Immunomodulation for Solid Organ Transplantation.

Husain, Irma / Luo, Xunrong

2023 Volume 75, Page(s) 369–380

Abstract: Despite significant advances in the field of transplantation in the past two decades, current clinically available therapeutic options for immunomodulation remain fairly limited. The advent of calcineurin inhibitor-based immunosuppression has led to ... ...

Abstract	Despite significant advances in the field of transplantation in the past two decades, current clinically available therapeutic options for immunomodulation remain fairly limited. The advent of calcineurin inhibitor-based immunosuppression has led to significant success in improving short-term graft survival; however, improvements in long-term graft survival have stalled. Solid organ transplantation provides a unique opportunity for immunomodulation of both the donor organ prior to implantation and the recipient post transplantation. Furthermore, therapies beyond targeting the adaptive immune system have the potential to ameliorate ischemic injury to the allograft and halt its aging process, augment its repair, and promote recipient immune tolerance. Other recent advances include expanding the donor pool by reducing organ discard, and bioengineering and genetically modifying organs from other species to generate transplantable organs. Therapies discussed here will likely be most impactful if individualized on the basis of specific donor and recipient considerations.
MeSH term(s)	Humans ; Immunomodulation ; Immune Tolerance ; Bioengineering ; Graft Survival ; Organ Transplantation
Language	English
Publishing date	2023-08-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	207930-6
ISSN	1545-326X ; 0066-4219
ISSN (online)	1545-326X
ISSN	0066-4219
DOI	10.1146/annurev-med-050522-034012
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Article ; Online: The T-cell environment: may the regulatory force be with you.

Luo, Xunrong / Knechtle, Stuart

Kidney international

2023 Volume 105, Issue 1, Page(s) 20–22

Abstract: In the study by Sasaki et al. in this issue, the authors studied infusions of ex vivo-expanded regulatory T cells in a highly clinically relevant nonhuman primate kidney transplant model. This commentary will aim to discuss the use of regulatory T cells ... ...

Abstract	In the study by Sasaki et al. in this issue, the authors studied infusions of ex vivo-expanded regulatory T cells in a highly clinically relevant nonhuman primate kidney transplant model. This commentary will aim to discuss the use of regulatory T cells in the wider context of transplantation, with particular emphasis on the milieu and various engineering potentials to enhance their function, as well as their relationship to other cell populations with regulatory capacity.
MeSH term(s)	Animals ; T-Lymphocytes, Regulatory ; Kidney Transplantation/adverse effects
Language	English
Publishing date	2023-11-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1016/j.kint.2023.10.023
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Zs.A 797: Show issues

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Article ; Online: Negative Vaccination Strategies for Promotion of Transplant Tolerance.

Tunbridge, Matthew J / Luo, Xunrong / Thomson, Angus W

Transplantation

2024

Abstract: Organ transplantation requires the use of immunosuppressive medications that lack antigen specificity, have many adverse side effects, and fail to induce immunological tolerance to the graft. The safe induction of tolerance to allogeneic tissue without ... ...

Abstract	Organ transplantation requires the use of immunosuppressive medications that lack antigen specificity, have many adverse side effects, and fail to induce immunological tolerance to the graft. The safe induction of tolerance to allogeneic tissue without compromising host responses to infection or enhancing the risk of malignant disease is a major goal in transplantation. One promising approach to achieve this goal is based on the concept of "negative vaccination." Vaccination (or actively acquired immunity) involves the presentation of both a foreign antigen and immunostimulatory adjuvant to the immune system to induce antigen-specific immunity. By contrast, negative vaccination, in the context of transplantation, involves the delivery of donor antigen before or after transplantation, together with a "negative adjuvant" to selectively inhibit the alloimmune response. This review will explore established and emerging negative vaccination strategies for promotion of organ or pancreatic islet transplant tolerance. These include donor regulatory myeloid cell infusion, which has progressed to early-phase clinical trials, apoptotic donor cell infusion that has advanced to nonhuman primate models, and novel nanoparticle antigen-delivery systems.
Language	English
Publishing date	2024-02-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	208424-7
ISSN	1534-6080 ; 0041-1337
ISSN (online)	1534-6080
ISSN	0041-1337
DOI	10.1097/TP.0000000000004911
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Article ; Online: Standardization and Interpretation of RNA-sequencing for Transplantation.

Thareja, Gaurav / Suryawanshi, Hemant / Luo, Xunrong / Muthukumar, Thangamani

Transplantation

2023 Volume 107, Issue 10, Page(s) 2155–2167

Abstract: RNA-sequencing (RNA-seq) is a technique to determine the order of nucleotides in an RNA segment. Modern sequencing platforms simultaneously sequence millions of RNA molecules. Advances in bioinformatics have allowed us to collect, store, analyze, and ... ...

Abstract	RNA-sequencing (RNA-seq) is a technique to determine the order of nucleotides in an RNA segment. Modern sequencing platforms simultaneously sequence millions of RNA molecules. Advances in bioinformatics have allowed us to collect, store, analyze, and disseminate data from RNA-seq experiments and decipher biological insights from large sequencing datasets. Although bulk RNA-seq has significantly advanced our understanding of tissue-specific gene expression and regulation, recent advances in single-cell RNA-seq have allowed such information to be mapped to individual cells, thus remarkably enhancing our insight into discrete cellular functions within a biospecimen. These different RNA-seq experimental approaches require specialized computational tools. Herein, we will first review the RNA-seq experimental workflow, discuss the common terminologies used in RNA-seq, and suggest approaches for standardization across multiple studies. Next, we will provide an up-to-date appraisal of the applications of bulk RNA-seq and single-cell/nucleus RNA-seq in preclinical and clinical research on kidney transplantation, as well as typical bioinformatic workflows utilized in such analysis. Lastly, we will deliberate on the limitations of this technology in transplantation research and briefly summarize newer technologies that could be combined with RNA-seq to permit more powerful dissections of biological functions. Because each step in RNA-seq workflow has numerous variations and could potentially impact the results, as conscientious citizens of the research community, we must strive to continuously modernize our analytical pipelines and exhaustively report their technical details.
MeSH term(s)	High-Throughput Nucleotide Sequencing/methods ; Sequence Analysis, RNA/methods ; Computational Biology/methods ; RNA/genetics ; Reference Standards ; Single-Cell Analysis
Chemical Substances	RNA (63231-63-0)
Language	English
Publishing date	2023-04-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	208424-7
ISSN	1534-6080 ; 0041-1337
ISSN (online)	1534-6080
ISSN	0041-1337
DOI	10.1097/TP.0000000000004558
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Article ; Online: Apoptotic Donor Cells in Transplantation.

Husain, Irma / Luo, Xunrong

Frontiers in immunology

2021 Volume 12, Page(s) 626840

Abstract: Despite significant advances in prevention and treatment of transplant rejection with immunosuppressive medications, we continue to face challenges of long-term graft survival, detrimental medication side effects to both the recipient and transplanted ... ...

Abstract	Despite significant advances in prevention and treatment of transplant rejection with immunosuppressive medications, we continue to face challenges of long-term graft survival, detrimental medication side effects to both the recipient and transplanted organ together with risks for opportunistic infections. Transplantation tolerance has so far only been achieved through hematopoietic chimerism, which carries with it a serious and life-threatening risk of graft versus host disease, along with variability in persistence of chimerism and uncertainty of sustained tolerance. More recently, numerous
MeSH term(s)	Animals ; Antigen-Presenting Cells/immunology ; Antigen-Presenting Cells/transplantation ; Apoptosis ; Cell- and Tissue-Based Therapy/methods ; Chimerism ; Graft Rejection/immunology ; Graft Rejection/prevention & control ; Graft vs Host Disease/immunology ; Graft vs Host Disease/prevention & control ; Humans ; Immunosuppressive Agents/therapeutic use ; Organ Transplantation ; Tissue Donors ; Transplantation Immunology ; Transplantation Tolerance ; Ureohydrolases/immunology
Chemical Substances	Immunosuppressive Agents ; Ureohydrolases (EC 3.5.3.-) ; allantoicase (EC 3.5.3.4)
Language	English
Publishing date	2021-02-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.626840
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Article ; Online: Conversion of CD73hiFR4hi anergic T cells to IFN-γ-producing effector cells disrupts established immune tolerance.

Dangi, Anil / Husain, Irma / Jordan, Collin Z / Yu, Shuangjin / Luo, Xunrong

The Journal of clinical investigation

2023 Volume 133, Issue 5

MeSH term(s)	T-Lymphocytes ; Clonal Anergy ; Immune Tolerance ; Lymphocytes
Language	English
Publishing date	2023-03-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI163872
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Article ; Online: Dissecting the human kidney allograft transcriptome: single-cell RNA sequencing.

Varma, Elly / Luo, Xunrong / Muthukumar, Thangamani

Current opinion in organ transplantation

2021 Volume 26, Issue 1, Page(s) 43–51

Abstract: Purpose of review: Single-cell RNA sequencing (scRNA-seq) has provided opportunities to interrogate kidney allografts at a hitherto unavailable molecular level of resolution. Understanding of this technology is essential to better appreciate the ... ...

Abstract	Purpose of review: Single-cell RNA sequencing (scRNA-seq) has provided opportunities to interrogate kidney allografts at a hitherto unavailable molecular level of resolution. Understanding of this technology is essential to better appreciate the relevant biomedical literature. Recent findings: Sequencing is a technique to determine the order of nucleotides in a segment of RNA or DNA. RNA-seq of kidney allograft tissues has revealed novel mechanistic insights but does not provide information on individual cell types and cell states. scRNA-seq enables to study the transcriptome of individual cells and assess the transcriptional differences and similarities within a population of cells. Initial studies on rejecting kidney allograft tissues in humans have identified the transcriptional profile of the active players of the innate and adaptive immune system. Application of scRNA-seq in a preclinical model of kidney transplantation has revealed that allograft-infiltrating myeloid cells follow a trajectory of differentiation from monocytes to proinflammatory macrophages and exhibit distinct interactions with kidney allograft parenchymal cells; myeloid cell expression of Axl played a major role in promoting intragraft myeloid cell and T-cell differentiation. Summary: The current review discusses the technical aspects of scRNA-seq and summarizes the application of this technology to dissect the human kidney allograft transcriptome.
MeSH term(s)	Allografts ; Biomarkers/metabolism ; Graft Rejection/metabolism ; Humans ; Kidney/immunology ; Kidney Transplantation ; Macrophages/metabolism ; Sequence Analysis, RNA/methods ; Single-Cell Analysis/methods ; Transcriptome/immunology ; Transplantation, Homologous
Chemical Substances	Biomarkers
Language	English
Publishing date	2021-01-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1390429-2
ISSN	1531-7013 ; 1087-2418
ISSN (online)	1531-7013
ISSN	1087-2418
DOI	10.1097/MOT.0000000000000840
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Zs.A 5609: Show issues

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Article ; Online: Cellular Therapies in Solid Organ Allotransplantation: Promise and Pitfalls.

Shaw, Brian I / Ord, Jeffrey R / Nobuhara, Chloe / Luo, Xunrong

Frontiers in immunology

2021 Volume 12, Page(s) 714723

Abstract: Donor specific transfusions have been the basis of tolerance inducing protocols since Peter Medawar showed that it was experimentally feasible in the 1950s. Though trials of cellular therapies have become increasingly common in solid organ ... ...

Abstract	Donor specific transfusions have been the basis of tolerance inducing protocols since Peter Medawar showed that it was experimentally feasible in the 1950s. Though trials of cellular therapies have become increasingly common in solid organ transplantation, they have not become standard practice. Additionally, whereas some protocols have focused on cellular therapies as a method for donor antigen delivery-thought to promote tolerance in and of itself in the correct immunologic context-other approaches have alternatively focused on the intrinsic immunosuppressive properties of the certain cell types with less emphasis on their origin, including mesenchymal stem cells, regulatory T cells, and regulatory dendritic cells. Regardless of intent, all cellular therapies must contend with the potential that introducing donor antigen in a new context will lead to sensitization. In this review, we focus on the variety of cellular therapies that have been applied in human trials and non-human primate models, describe their efficacy, highlight data regarding their potential for sensitization, and discuss opportunities for cellular therapies within our current understanding of the immune landscape.
MeSH term(s)	Animals ; Cell- and Tissue-Based Therapy/adverse effects ; Cell- and Tissue-Based Therapy/methods ; Cell- and Tissue-Based Therapy/trends ; Combined Modality Therapy ; Graft Rejection/immunology ; Graft Survival/immunology ; Hematopoietic Stem Cell Transplantation ; Humans ; Immune Tolerance ; Immunosuppression Therapy ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/metabolism ; Organ Transplantation/adverse effects ; Organ Transplantation/methods ; Organ Transplantation/trends ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; Tissue Donors ; Transplantation, Homologous
Language	English
Publishing date	2021-08-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.714723
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Article: Development and Validation of a Radiomics Nomogram for Predicting Clinically Significant Prostate Cancer in PI-RADS 3 Lesions.

Li, Tianping / Sun, Linna / Li, Qinghe / Luo, Xunrong / Luo, Mingfang / Xie, Haizhu / Wang, Peiyuan

Frontiers in oncology

2022 Volume 11, Page(s) 825429

Abstract: Purpose: To develop and validate a radiomics nomogram for the prediction of clinically significant prostate cancer (CsPCa) in Prostate Imaging-Reporting and Data System (PI-RADS) category 3 lesions.: Methods: We retrospectively enrolled 306 patients ... ...

Abstract	Purpose: To develop and validate a radiomics nomogram for the prediction of clinically significant prostate cancer (CsPCa) in Prostate Imaging-Reporting and Data System (PI-RADS) category 3 lesions. Methods: We retrospectively enrolled 306 patients within PI-RADS 3 lesion from January 2015 to July 2020 in institution 1; the enrolled patients were randomly divided into the training group (n = 199) and test group (n = 107). Radiomics features were extracted from T2-weighted imaging (T2WI), apparent diffusion coefficient (ADC) imaging, and dynamic contrast-enhanced (DCE) imaging. Synthetic minority oversampling technique (SMOTE) was used to address the class imbalance. The ANOVA and least absolute shrinkage and selection operator (LASSO) regression model were used for feature selection and radiomics signature building. Then, a radiomics score (Rad-score) was acquired. Combined with serum prostate-specific antigen density (PSAD) level, a multivariate logistic regression analysis was used to construct a radiomics nomogram. Receiver operating characteristic (ROC) curve analysis was used to evaluate radiomics signature and nomogram. The radiomics nomogram calibration and clinical usefulness were estimated through calibration curve and decision curve analysis (DCA). External validation was assessed, and the independent validation cohort contained 65 patients within PI-RADS 3 lesion from January 2020 to July 2021 in institution 2. Results: A total of 75 (24.5%) and 16 (24.6%) patients had CsPCa in institution 1 and 2, respectively. The radiomics signature with SMOTE augmentation method had a higher area under the ROC curve (AUC) [0.840 (95% CI, 0.776-0.904)] than that without SMOTE method [0.730 (95% CI, 0.624-0.836), Conclusion: The radiomics nomogram that incorporates the MRI-based radiomics signature and PSAD can be conveniently used to individually predict CsPCa in patients within PI-RADS 3 lesion.
Language	English
Publishing date	2022-01-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2021.825429
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Article ; Online: Joining Forces in Basic Science: ITS Meeting 2.0.

Pilat, Nina / Issa, Fadi / Luo, Xunrong / Chong, Anita / Bromberg, Jonathan / Kotsch, Katja

Transplant international : official journal of the European Society for Organ Transplantation

2022 Volume 35, Page(s) 10843

Abstract: The second International Transplant Science (ITS) meeting jointly organized by the European Society for Organ Transplantation (ESOT), the American Society of Transplantation (AST), and The Transplantation Society (TTS) took place in May 2022 in one of ... ...

Abstract	The second International Transplant Science (ITS) meeting jointly organized by the European Society for Organ Transplantation (ESOT), the American Society of Transplantation (AST), and The Transplantation Society (TTS) took place in May 2022 in one of Europe's most iconic cities: Berlin, Germany. The ITS meeting 2022 was designed to serve as an international platform for scientific discussions on the latest ground-breaking discoveries in the field, while providing an excellent opportunity to present cutting-edge research to the scientific community. We think this is fundamental for the exchange of new ideas and establishment of collaborative work between advanced transplant experts, young professionals and early-stage researchers and students. Scientific sessions tackled hot topics in transplantation such as mechanisms of tolerance, biomarkers, big data and artificial intelligence. Our educational pre-meeting focused on the breakthrough and challenges in single-cell multimodal omics. The program included panel discussions illuminating various topics concerning conflicts and problems related to gender, such as challenges for female scientists. Attendees returned to their institutes with not only profound knowledge of the latest discoveries, technologies, and concepts in basic and translational science, but also inspired and excited after discussions and networking sessions with fellow scientists which have been duly missed during the pandemic.
MeSH term(s)	Artificial Intelligence ; Female ; Germany ; Humans ; Immune Tolerance ; Organ Transplantation ; Transplants
Language	English
Publishing date	2022-09-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	639435-8
ISSN	1432-2277 ; 0934-0874
ISSN (online)	1432-2277
ISSN	0934-0874
DOI	10.3389/ti.2022.10843
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