Calcineurin Inhibitors Suppress Acute Graft-vs-Host Disease via NFAT-Independent Inhibition of T Cell Receptor Signaling

Researchers utilized T cells from mice that express LckS59A, which cannot accept a phosphate at residue 59, to initiate acute graft-versus-host disease.
[Journal of Clinical Investigation]
Otsuka, S., Melis, N., Gaida, M. M., Dutta, D., Weigert, R., & Ashwell, J. D. (2021). Calcineurin inhibitors suppress acute graft-vs-host disease via NFAT-independent inhibition of T cell receptor signaling. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI147683 Cite
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Chimeric CTLA4-CD28-CD3z T Cells Potentiate Antitumor Activity against CD80/CD86–Positive B Cell Malignancies

CTLA4-chimeric antigen receptor T cells were found to accumulate in tumors and are toxic to myeloid-derived suppressor cells without signs of severe GVHD and CRS in preclinical models.
[Frontiers in Immunology]
Lin, S., Cheng, L., Ye, W., Li, S., Zheng, D., Qin, L., Wu, Q., Long, Y., Lin, S., Wang, S., Huang, G., Li, P., Yao, Y., & Sun, X. (2021). Chimeric CTLA4-CD28-CD3z T Cells Potentiate Antitumor Activity Against CD80/CD86–Positive B Cell Malignancies. Frontiers in Immunology, 12. https://doi.org/10.3389/fimmu.2021.642528 Cite
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Outcome of T-Cell-Replete Haploidentical Stem Cell Transplantation Improves with Time in Adults with Acute Lymphoblastic Leukemia: A Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

The Acute Leukemia Working Party/European Society for Blood and Marrow Transplantation registry was used to evaluate the outcomes of adult patients with acute lymphoblastic leukemia who underwent hematopoietic cell transplantation during 2011 through 2015 and compared them with the outcomes of those who underwent transplantation during 2016 through 2018.
[Cancer]
Nagler, A., Labopin, M., Koc, Y., Angelucci, E., Tischer, J., Arat, M., Pioltelli, P., Bernasconi, P., Chiusolo, P., Diez‐Martin, J. L., Sanz, J., Ciceri, F., Peric, Z., Giebel, S., Canaani, J., & Mohty, M. (n.d.). Outcome of T-cell–replete haploidentical stem cell transplantation improves with time in adults with acute lymphoblastic leukemia: A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Cancer, n/a(n/a). https://doi.org/https://doi.org/10.1002/cncr.33522 Cite
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Wnt/β-Catenin Signaling Mediates the Abnormal Osteogenic and Adipogenic Capabilities of Bone Marrow Mesenchymal Stem Cells from Chronic Graft-versus-Host Disease Patients

Scientists analyzed bone marrow-MSCs from 66 patients after allo-hematopoietic stem cell transplantation, including 33 with active chronic graft-versus-host disease and 33 without chronic graft-versus-host disease.
[Cell Death & Disease]
Qi, H., Ye, Y., Suo, Y., Qu, H., Zhang, H., Yang, K., Fan, Z., Huang, F., Xuan, L., Chen, Y., Jin, H., & Liu, Q. (2021). Wnt/β-catenin signaling mediates the abnormal osteogenic and adipogenic capabilities of bone marrow mesenchymal stem cells from chronic graft-versus-host disease patients. Cell Death & Disease, 12(4), 1–13. https://doi.org/10.1038/s41419-021-03570-6 Cite
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Current Status and Perspective of CAR-T and CAR-NK Cell Therapy Trials in Germany

The authors take a closer look at the commercial CAR-T cell therapies, as well as on CAR-T and CAR-NK cell products, which are currently under evaluation in clinical trials, that are being conducted in Germany.
[Gene Therapy]
Albinger, N., Hartmann, J., & Ullrich, E. (2021). Current status and perspective of CAR-T and CAR-NK cell therapy trials in Germany. Gene Therapy, 1–15. https://doi.org/10.1038/s41434-021-00246-w Cite
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Mesenchymal Stem/Stromal Cells as a Valuable Source for the Treatment of Immune-Mediated Disorders

The authors discuss the therapeutic applications of mesenchymal stem/stromal cell (MSC) secretome and its biomedical aspects related to immune-mediated conditions. Sources for MSC extraction, their migration and homing properties, therapeutic molecules released by MSCs, and the pathways and molecular mechanisms possibly involved in the exceptional immunoregulatory competence of MSCs are discussed.
[Stem Cell Research & Therapy]
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RNA-Seq of Human T Cells after Hematopoietic Stem Cell Transplantation Identifies Linc00402 as a Regulator of T Cell Alloimmunity

Linc00402 was increased in donor T cells from patients who underwent allogeneic cardiac transplantation and in murine T cells.
[Science Translational Medicine]
Peltier, D., Radosevich, M., Ravikumar, V., Pitchiaya, S., Decoville, T., Wood, S. C., Hou, G., Zajac, C., Oravecz-Wilson, K., Sokol, D., Henig, I., Wu, J., Kim, S., Taylor, A., Fujiwara, H., Sun, Y., Rao, A., Chinnaiyan, A. M., Goldstein, D. R., & Reddy, P. (2021). RNA-seq of human T cells after hematopoietic stem cell transplantation identifies Linc00402 as a regulator of T cell alloimmunity. Science Translational Medicine, 13(585). https://doi.org/10.1126/scitranslmed.aaz0316 Cite
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Contemporary Haploidentical Stem Cell Transplant Strategies in Children with Hematological Malignancies

While comparing the outcomes of different haploidentical hematopoietic stem cell transplantation approaches, one must understand the transplant immunobiology and factors affecting the transplant outcomes.
[Bone Marrow Transplantation]
Shah, R. M. (2021). Contemporary haploidentical stem cell transplant strategies in children with hematological malignancies. Bone Marrow Transplantation, 1–17. https://doi.org/10.1038/s41409-021-01246-5 Cite
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High Proportion of Terminally Differentiated Regulatory T Cells after Allogeneic Hematopoietic Stem Cell Transplantation

Scientists compared the frequencies of different regulatory T cell subtypes in healthy controls as well as in allogeneic hematopoietic cell transplantation patients with or without chronic graft-versus-host disease.
[Bone Marrow Transplantation]
Ritacco, C., Ehx, G., Grégoire, C., Daulne, C., Willems, E., Servais, S., Beguin, Y., & Baron, F. (2021). High proportion of terminally differentiated regulatory T cells after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplantation, 1–14. https://doi.org/10.1038/s41409-021-01221-0 Cite
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Effect of Methotrexate Dose in Graft-versus-Host Disease Prophylaxis after Single-Unit Cord Blood Transplantation in Adult Acute Myeloid Leukemia

The authors investigated the association between methotrexate dosage and engraftment, graft-versus-host disease (GVHD) incidence, and survival in umbilical cord blood transplantation, and compared transplant outcomes after UCBT with various GVHD prophylaxis regimens, using registry data with additional data collection.
[International Journal of Hematology]
Terakura, S., Kuwatsuka, Y., Sugita, J., Takahashi, S., Ozawa, Y., Ozeki, K., Yoshioka, S., Nakamae, H., Kawakita, T., Sawa, M., Morishige, S., Najima, Y., Katsuoka, Y., Sakaida, E., Kouzai, Y., Kimura, T., Ichinohe, T., Fukuda, T., Atsuta, Y., … Teshima, T. (2021). Effect of methotrexate dose in graft-versus-host disease prophylaxis after single-unit cord blood transplantation in adult acute myeloid leukemia. International Journal of Hematology. https://doi.org/10.1007/s12185-021-03097-8 Cite
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Gene Editing Rescues In vitro T Cell Development of RAG2-Deficient Induced Pluripotent Stem Cells in an Artificial Thymic Organoid System

Using patient-derived iPSCs and an in vitro artificial thymic organoid system as a model, investigators demonstrate that gene editing rescued the progressive T cell differentiation potential of RAG2-deficient cells to normal levels, with generation of a diversified T cell repertoire.
[Journal of Clinical Immunology]
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