Review
Immunology
Matteo Doglio, Rachel E. E. Crossland, Ana C. C. Alho, Olaf Penack, Anne M. M. Dickinson, Georg Stary, Joao F. Lacerda, Gunther Eissner, Marit Inngjerdingen
Summary: This review discusses immunomodulatory approaches for the prevention and treatment of chronic graft-versus-host disease (cGVHD), including T cells, NK cells, ILCs, MSCs, and extracellular vesicles. Clinical studies and pre-clinical research results are presented.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Xianjing Cheng, Ruihao Huang, Shiqin Huang, Wei Fan, Rongdi Yuan, Xiaoqi Wang, Xi Zhang
Summary: Ocular graft-versus-host disease (GVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation. It greatly impacts the quality of life of affected individuals due to impaired visual function, pain, and other symptoms. However, the diagnosis and treatment of ocular GVHD pose challenges for hematologists and ophthalmologists, as there are no unified international criteria. This review explores the complex pathogenesis of ocular GVHD, providing a comprehensive summary of the disease's pathogenic mechanisms, related tear biomarkers, and clinical characteristics. Novel therapies based on these mechanisms are also discussed, offering new insights into ocular GVHD treatment.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Fathima A. Mohamed, Govindarajan Thangavelu, Stephanie Y. Rhee, Peter T. Sage, Roddy S. O'Connor, Jeffrey C. Rathmell, Bruce R. Blazar
Summary: The therapeutic efficacy of allo-HSCT is limited by the development of GVHD, with immune dysregulation leading to expansion of alloreactive cells and reduction in regulatory cells. New therapies are needed to restore the balance between effector and regulatory immune cells while preserving the beneficial graft-versus-tumor effect.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biophysics
Alexandra A. Pietraszkiewicz, Debbie Payne, Maria Abraham, Angel Garced, Krishna C. Devarasetty, Megan Wall, Supriya M. Menezes, Sveti Ugarte, Filip Pirsl, Sencer Goklemez, Frederick L. Ferris, John Barrett, Minoo Battiwalla, Richard W. Childs, Steven Z. Pavletic, Rachel J. Bishop
Summary: The study found a tendency towards ocular dryness in individuals with hematologic disorders preparing for HSCT based on differences in baseline ocular surface indicators; individuals who developed oGVHD showed changes in corneal staining score, Schirmer's test, and TBUT.
BONE MARROW TRANSPLANTATION
(2021)
Review
Hematology
Noa G. Holtzman, Steven Z. Pavletic
Summary: Chronic graft-versus-host disease (cGVHD) is a systemic complication of allogeneic haematopoietic stem cell transplantation that can lead to increased morbidity and mortality. Despite limited curative treatment options, recent collaborative research efforts have led to discovery of new second-line therapies. Comprehensive and sustained multidisciplinary efforts are crucial for successful management of cGVHD.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Chemistry, Medicinal
Andrey Kozlov, Maria Estrina, Olesia Paina, Tatiana Bykova, Anna Osipova, Polina Kozhokar, Zhemal Rakhmanova, Irina Solodova, Elena Morozova, Alexander Alyansky, Irina Kulagina, Asmik Gevorgian, Anna Dotsenko, Ivan Moiseev, Alexey Chukhlovin, Alexander Kulagin, Sergey Bondarenko, Elena Semenova, Ludmila Zubarovskaya
Summary: This study investigated the efficacy and safety of extracorporeal photopheresis (ECP) in children with chronic graft versus host disease (cGVHD). The results showed that a portion of patients responded partially or completely to ECP treatment, with a certain survival rate within 5 years.
Article
Medicine, General & Internal
Purwa Joshi, Lynette Kiers, Andrew Evans, David Ritchie, Jeff Szer, Belinda Cruse
Summary: The article describes five patients with cGVHD presenting with oromandibular parafunction, discussing the pathophysiological mechanisms and the efficacy of targeted botulinum toxin injections with minimal side effects.
INTERNAL MEDICINE JOURNAL
(2021)
Review
Immunology
Laura Marie Gail, Kimberly Julia Schell, Piotr Lacina, Johanna Strobl, Steven J. Bolton, Emilie Steinbakk Ulriksen, Katarzyna Bogunia-Kubik, Hildegard Greinix, Rachel Emily Crossland, Marit Inngjerdingen, Georg Stary
Summary: Chronic Graft-versus-Host Disease (cGVHD) is a life-threatening inflammatory condition occurring after allogeneic hematopoietic stem cell transplantation. Despite progress in understanding disease pathogenesis, treatment options remain limited. This review provides an overview of the pathogenic and protective mechanisms involving immune subsets, as well as the emerging field of intercellular communication via extracellular vesicles and its implications for cGVHD research. The importance of understanding aberrant cell communication for biomarker discovery and personalized treatment is discussed.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Shinri Sato, Eisuke Shimizu, Jingliang He, Mamoru Ogawa, Kazuki Asai, Hiroyuki Yazu, Robert Rusch, Mio Yamane, Fan Yang, Shinji Fukuda, Yutaka Kawakami, Kazuo Tsubota, Yoko Ogawa
Summary: In this study, it was found in a mouse model that gentamicin (GM) significantly suppressed systemic cGVHD phenotypes and ocular manifestations, and reduced inflammatory cell infiltration and fibrosis in cGVHD-targeted organs. Although GM maintained higher levels of regulatory T cells, there were fewer Th17 cells and IL-6-producing macrophages in cGVHD-targeted organs. These findings suggest that orally administered GM may have positive effects in a cGVHD mouse model.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Lydia Verlaat, Katarina Riesner, Martina Kalupa, Beate Jung, Sarah Mertlitz, Constanze Schwarz, Joerg Mengwasser, Claudine Fricke, Olaf Penack
Summary: Despite progress in allo-HCT, cGvHD remains a major hurdle, and improved pre-clinical models are needed. We developed two murine cGvHD models that resemble the clinical manifestations of cGvHD in patients. These models exhibited diverse signs of cGvHD in target organs and decelerated immune cell reconstitution. They can provide a deeper understanding of cGvHD pathology and facilitate the translation of experimental findings into human allo-HCT.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Hematology
Michael Pratta, Sophie Paczesny, Gerard Socie, Natalie Barkey, Hao Liu, Sherry Owens, Michael C. Arbushites, Mark A. Schroeder, Michael D. Howell
Summary: This study identified 7 candidate biomarkers using a broad proteomic analysis, in which MCP3, ProCALCA/CALCA, and REG3A could stratify responders and non-responders to itacitinib in acute GVHD, while ProCALCA/CALCA, ST2, and TNFR1 could serve as response-to-treatment biomarkers.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Review
Immunology
Chao Hong, Rong Jin, Xiaoqiu Dai, Xiaoming Gao
Summary: Chronic graft-versus-host disease (cGVHD) is a common cause of late morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). The pathogenesis of cGVHD is complex and involves a variety of immune cells, with antigen presenting cells (APCs) playing crucial roles in presenting antigens to activate pathogenic T cells and mediating the disease through multiple mechanisms. Studies targeting different APCs have shown promising results in treating cGVHD.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Yiwen Liang, Jingyi Shen, Qiu Lan, Kexin Zhang, Yan Xu, Maxwell Duah, Kailin Xu, Bin Pan
Summary: This research found that PD-1 expression on T cells increased in mice with chronic graft-versus-host disease (cGVHD). Intervention of the PD-1/PD-L1 pathway showed a significant impact on the occurrence of cGVHD and graft-versus-tumor effect.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Review
Oncology
Ori Bar, Sharon Elad, Batia Avni, Jawad Abu-Tair, Bianca Zaharia, Aiham Hanut, Yehuda Zadik
Summary: This study presented new cases of oral VX in chronic graft-versus-host disease (cGVHD) and reviewed relevant literature, identifying 12 patients with OVX. Most patients had oral mucosal lichenoid lesions, but not in close proximity to the VX lesion. It is recommended that clinicians be familiar with the clinical and histological features of OVX to consider it in the differential diagnosis of oral lesions in cGVHD patients.
SUPPORTIVE CARE IN CANCER
(2021)
Article
Hematology
Divya Subburaj, Bernard Ng, Amina Kariminia, Sayeh Abdossamadi, Madeline Lauener, Eneida R. Nemecek, Jacob Rozmus, Sandhya Kharbanda, Carrie L. Kitko, Victor A. Lewis, Tal Schechter-Finklestein, David A. Jacobsohn, Andrew C. Harris, Michael A. Pulsipher, Henrique Bittencourt, Sung Won Choi, Emi H. Caywood, Kimberly A. Kasow, Monica Bhatia, Benjamin R. Oshrine, Donald Coulter, Joseph H. Chewning, Michael Joyce, Anna B. Pawlowska, Gail C. Megason, Anita Lawitschka, Elena Ostroumov, Ramon Klein Geltink, Geoffrey D. E. Cuvelier, Kirk R. Schultz
Summary: This study longitudinally evaluated the metabolomic patterns of chronic graft-versus-host disease (cGVHD) and late acute graft-versus-host disease (aGVHD) in pediatric hematopoietic stem cell transplant recipients. The results showed that plasma alpha-ketoglutaric acid levels were consistently elevated before and at the onset of cGVHD, and late aGVHD had a unique metabolomic pattern at an early stage compared to cGVHD.
Article
Dermatology
Ashley E. Stenzel, Jonathan Miller, Shernan G. Holtan, Katherine Brown, Rehana L. Ahmed, DeAnn Lazovich, Rachel Vogel
Summary: Long-term melanoma survivors are more likely to meet American Cancer Society physical activity guidelines than population controls, but almost 50% do not meet the recommendations. This finding is concerning as physical activity is known to improve quality of life and survival among cancer survivors. There are still opportunities to promote physical activity among melanoma survivors.
ARCHIVES OF DERMATOLOGICAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Emma Proics, Marion David, Majid Mojibian, Madeline Speck, Nadia Lounnas-Mourey, Adeline Govehovitch, Wissam Baghdadi, Justine Desnouveaux, Herve Bastian, Laura Freschi, Geoffrey Privat, Cedric Pouzet, Mauro Grossi, Pierre Heimendinger, Tobias Abel, David Fenard, Megan K. Levings, Francois Meyer, Celine Dumont
Summary: This publication reports the preclinical characterization of Tregs transduced with a CAR lentiviral vector. The results demonstrated the specificity, immunosuppressive function, and safety of the transduced Tregs. The study also showed that the transduced Tregs effectively prevented graft-versus-host disease in mice and remained stable without switching to a proinflammatory phenotype. Furthermore, concomitant tacrolimus did not impair the survival or inhibitory function of the transduced Tregs.
Article
Biophysics
Ana Zelic Kerep, Atillio Olivieri, Helene Schoemans, Anita Lawitschka, Joerg Halter, Drazen Pulanic, Anne Dickinson, Hildegard T. Greinix, Steven Z. Pavletic, Kirk R. Schultz, Stephanie J. Lee, Daniel Wolff
Summary: The article introduces the formation and content of the cGVHD dictionary, aiming to provide a standardized structure for international databases and facilitate data retrieval and merging.
BONE MARROW TRANSPLANTATION
(2023)
Review
Endocrinology & Metabolism
Adam Ramzy, Paul J. Belmonte, Mitchell J. S. Braam, Shogo Ida, Emily M. Wilts, Megan K. Levings, Alireza Rezania, Timothy J. Kieffer
Summary: Insulin injections have saved many lives, but glycemic instability remains a challenge for people with diabetes. Islet transplantation research suggests that replacing insulin-producing beta cells can restore normal blood sugar levels. Pluripotent stem cells could provide an unlimited supply of beta cells, but more research and development is needed.
Article
Immunology
Dominic A. Boardman, May Q. Wong, William D. Rees, Dan Wu, Megan E. Himmel, Paul C. Orban, Jens Vent-Schmidt, Nicholas C. Zachos, Theodore S. Steiner, Megan K. Levings
Summary: Regulatory T cell (Treg) therapy is a promising strategy for treating inflammatory bowel disease (IBD). A novel chimeric antigen receptor (CAR) specific for flagellin derived from Escherichia coli H18 (FliC) was developed to confer FliC-specificity to human Tregs. FliC-CAR Tregs showed specificity and functionality, and demonstrated potential in treating IBD by suppressing inflammation and promoting the establishment of colon-derived epithelial cell monolayers.
JOURNAL OF AUTOIMMUNITY
(2023)
Editorial Material
Surgery
Manjurul Haque, Dominic A. Boardman, Megan K. Levings
AMERICAN JOURNAL OF TRANSPLANTATION
(2023)
Review
Immunology
Torin Halvorson, Karoliina Tuomela, Megan K. Levings
Summary: Regulatory T cells (Tregs) are important for maintaining immune homeostasis, but they can also hinder anti-tumor immunity. Targeting metabolic pathways can selectively promote or inhibit Treg function, offering potential therapeutic opportunities. This review explores the current understanding of Treg metabolism and discusses emerging metabolic targeting strategies in transplantation, autoimmunity, and cancer. Manipulating Treg metabolism during ex vivo expansion for adoptive cell therapy (ACT) and modulating Treg metabolism in disease states through nutritional and pharmacological interventions are also discussed.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Editorial Material
Immunology
Karoliina Tuomela, Megan K. Levings
Summary: A recent study reveals that lactic acid, through a pH-dependent mechanism, promotes the differentiation of conventional CD4(+) T cells into Tregs, contributing to the accumulation of Tregs within tumors. This finding adds to the understanding of lactic acid's role in maintaining an immunosuppressive tumor microenvironment.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Hematology
Shima Azadpour, Sayeh Abdossamadi, Bernard Ng, Elena Ostroumov, Saeid Abroun, Geoffrey D. E. Cuvelier, Kirk R. Schultz
EXPERIMENTAL HEMATOLOGY
(2023)
Review
Immunology
Karoliina Tuomela, Kevin Salim, Megan K. Levings
Summary: Regulatory T cells (Tregs) have been recognized as critical cells for immune homeostasis regulation. The development of designer Tregs has gone through three eras: FOXP3 engineering, antigen-specificity, and advanced genome-editing techniques, providing new opportunities for treating immune-mediated diseases.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Immunology
Esther Bernaldo-de-Quiros, Manuela Camino, Marta Martinez-Bonet, Juan Miguel Gil-Jaurena, Nuria Gil, Diana Hernandez-Florez, Maria Eugenia Fernandez-Santos, Laura Butragueno, I. Esme Dijke, Megan K. Levings, Lori J. West, Marjorie Pion, Rafael Correa-Rocha
Summary: This study developed a new approach to obtain large quantities of high-purity Tregs from routine surgeries, which could be used for cellular therapy to prevent transplant rejection. The initial results of the clinical trial showed that the administration of thyTregs in infants undergoing heart transplantation had no adverse effects and maintained a stable Treg frequency in the peripheral blood.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Immunology
Cara E. Ellis, Majid Mojibian, Shogo Ida, Vivian C. W. Fung, Sos Skovso, Emma McIver, Shannon O'Dwyer, Travis D. Webber, Mitchell J. S. Braam, Nelly Saber, Shugo Sasaki, Francis C. Lynn, Timothy J. Kieffer, Megan K. Levings
Summary: This study used A2-CAR T cells to investigate the rejection of insulin-producing cells and successfully addressed the issue of complications from xenogeneic graft-versus-host disease.
Article
Hematology
Sarah M. Bowers, Bernard Ng, Sayeh Abdossamadi, Amina Kariminia, David A. Cabral, Geoffrey D. E. Cuvelier, Kirk R. Schultz, Kelly L. Brown
Summary: Adenosinergic signaling has context-specific effects on immune cells, particularly on lymphocytes. Changes in ADA2 enzyme activity may be associated with the onset of chronic GVHD.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)
Article
Oncology
Chia Huan Ng, Juliana P. Roden, Jefferson Terry, Kirk R. Schultz
Summary: This case report describes three cases of penile chronic GvHD in adolescent male patients who received HSCT before puberty. The symptoms of penile cGvHD became evident during puberty, along with fibrotic changes in the foreskin. Circumcision was required for symptom relief in these patients. The report highlights the importance of frequent monitoring of prepubertal pediatric HSCT patients with sclerotic cGvHD who enter puberty, and the need for optimized systemic and topical immunosuppression treatment.
PEDIATRIC HEMATOLOGY AND ONCOLOGY
(2023)
Article
Medicine, Research & Experimental
Justin A. Spanier, Vivian Fung, Christine M. Wardell, Mohannad H. Alkhatib, Yixin Chen, Linnea A. Swanson, Alexander J. Dwyer, Matthew E. Weno, Nubia Silva, Jason S. Mitchell, Paul C. Orban, Majid Mojibian, C. Bruce Verchere, Brian T. Fife, Megan K. Levings
Summary: Engineering Tregs with specific recognition for islet antigens using a chimeric antigen receptor (CAR) is a promising therapeutic approach for preventing autoimmune diabetes.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
