20 results found
Pirillo C, Birch F, Tissot FS, et al., 2022, Metalloproteinase inhibition reduces AML growth, prevents stem cell loss, and improves chemotherapy effectiveness, BLOOD ADVANCES, Vol: 6, Pages: 3126-3141, ISSN: 2473-9529
Haltalli MLR, Watcham S, Wilson NK, et al., 2020, Manipulating niche composition limits damage to haematopoietic stem cells during Plasmodium infection, Nature Cell Biology, Vol: 22, Pages: 1399-1410, ISSN: 1465-7392
Severe infections are a major stress on haematopoiesis, where the consequences for haematopoietic stem cells (HSCs) have only recently started to emerge. HSC function critically depends on the integrity of complex bone marrow (BM) niches; however, what role the BM microenvironment plays in mediating the effects of infection on HSCs remains an open question. Here, using a murine model of malaria and combining single-cell RNA sequencing, mathematical modelling, transplantation assays and intravital microscopy, we show that haematopoiesis is reprogrammed upon infection, whereby the HSC compartment turns over substantially faster than at steady-state and HSC function is drastically affected. Interferon is found to affect both haematopoietic and mesenchymal BM cells and we specifically identify a dramatic loss of osteoblasts and alterations in endothelial cell function. Osteo-active parathyroid hormone treatment abolishes infection-triggered HSC proliferation and—coupled with reactive oxygen species quenching—enables partial rescuing of HSC function.
Pospori C, Grey W, Gibson S, et al., 2020, DYNAMIC REGULATION OF HIERARCHICAL HETEROGENEITY IN ACUTE MYELOID LEUKAEMIA, SERVES AS A TUMOUR IMMUNOEVASION MECHANISM., EXPERIMENTAL HEMATOLOGY, Vol: 88, Pages: S75-S75, ISSN: 0301-472X
Batsivari A, Haltalli MLR, Passaro D, et al., 2020, Dynamic responses of the haematopoietic stem cell niche to diverse stresses (vol 57, pg 1052, 2019), NATURE CELL BIOLOGY, Vol: 22, Pages: 257-257, ISSN: 1465-7392
Batsivari A, Haltalli MLR, Passaro D, et al., 2020, Dynamic responses of the haematopoietic stem cell niche to diverse stresses, NATURE CELL BIOLOGY, Vol: 22, Pages: 7-17, ISSN: 1465-7392
Burt R, Dey A, Aref S, et al., 2019, Activated stromal cells transfer mitochondria to rescue acute lymphoblastic leukemia cells from oxidative stress, BLOOD, Vol: 134, Pages: 1415-1429, ISSN: 0006-4971
Khan AB, Carpenter B, Santos e Sousa P, et al., 2018, Redirection to the bone marrow improves T cell persistence and antitumor functions, Journal of Clinical Investigation, Vol: 128, Pages: 2010-2024, ISSN: 0021-9738
A key predictor for the success of gene-modified T cell therapies for cancer is the persistence of transferred cells in the patient. The propensity of less differentiated memory T cells to expand and survive efficiently has therefore made them attractive candidates for clinical application. We hypothesized that redirecting T cells to specialized niches in the BM that support memory differentiation would confer increased therapeutic efficacy. We show that overexpression of chemokine receptor CXCR4 in CD8+ T cells (TCXCR4) enhanced their migration toward vascular-associated CXCL12+ cells in the BM and increased their local engraftment. Increased access of TCXCR4 to the BM microenvironment induced IL-15–dependent homeostatic expansion and promoted the differentiation of memory precursor–like cells with low expression of programmed death-1, resistance to apoptosis, and a heightened capacity to generate polyfunctional cytokine-producing effector cells. Following transfer to lymphoma-bearing mice, TCXCR4 showed a greater capacity for effector expansion and better tumor protection, the latter being independent of changes in trafficking to the tumor bed or local out-competition of regulatory T cells. Thus, redirected homing of T cells to the BM confers increased memory differentiation and antitumor immunity, suggesting an innovative solution to increase the persistence and functions of therapeutic T cells.
Xue S-A, Gao L, Ahmadi M, et al., 2013, Human MHC Class I-restricted high avidity CD4(+) T cells generated by co-transfer of TCR and CD8 mediate efficient tumor rejection in vivo, ONCOIMMUNOLOGY, Vol: 2, ISSN: 2162-402X
Xue SA, Gao L, Ahmadi M, et al., 2011, Generation of MHC-I restricted CD4+CMV and EBV specific T cells for the management of leukaemia patients, Publisher: MARY ANN LIEBERT INC, Pages: A73-A73, ISSN: 1043-0342
Xue S, Gao L, Ghorashian S, et al., 2011, GENERATION OF MHC-I RESTRICTED CD4+CMV SPECIFIC T CELLS FOR THE MANAGEMENT OF LEUKEMIA PATIENTS, Publisher: ELSEVIER SCIENCE INC, Pages: S65-S66, ISSN: 0301-472X
Pospori C, Xue S-A, Holler A, et al., 2011, Specificity for the tumor-associated self-antigen WT1 drives the development of fully functional memory T cells in the absence of vaccination, BLOOD, Vol: 117, Pages: 6813-6824, ISSN: 0006-4971
Xue SA, Ghorashian S, Pospori C, et al., 2010, Development of CMV-specific T cells for the management of transplantation patients, 18th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy, Publisher: MARY ANN LIEBERT INC, Pages: 1422-1423, ISSN: 1043-0342
Pospori C, Xue SA, Holler A, et al., 2010, Specificity for a tumor-associated self-antigen drives the development of functional memory T cells in the absence of vaccination, 18th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy, Publisher: MARY ANN LIEBERT INC, Pages: 1365-1366, ISSN: 1043-0342
Pospori C, Xue S-A, Holler A, et al., 2010, Adoptive immunotherapy with TCR-transferred lymphocytes, 18th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy, Publisher: MARY ANN LIEBERT INC, Pages: 1379-1379, ISSN: 1043-0342
Perro M, Tsang J, Xue S-A, et al., 2010, Generation of multi-functional antigen-specific human T-cells by lentiviral TCR gene transfer, GENE THERAPY, Vol: 17, Pages: 721-732, ISSN: 0969-7128
Xue SA, Gao L, Pospori C, et al., 2010, Development of Virus Specific T Cells for the Management of Leukaemia Patients, 7th Annual Conference of the British-Society-for-Gene-Therapy, Publisher: MARY ANN LIEBERT INC, Pages: 510-510, ISSN: 1043-0342
Pospori C, Cesco-Gaspere M, Xue S, et al., 2009, WT1-TCR gene transfer into haematopoietic stem cells: a tumour immunotherapy model, 35th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation, Publisher: NATURE PUBLISHING GROUP, Pages: S72-S72, ISSN: 0268-3369
Pospori C, Cesco-Gaspere M, Xue S, et al., 2009, WT1-TCR gene transfer into HSCs: a tumour immunotherapy model, 49th Annual Scientific Meeting of the British-Society-for-Haematology, Publisher: WILEY-BLACKWELL PUBLISHING, INC, Pages: 1-2, ISSN: 0007-1048
Stauss HJ, Thomas S, Cesco-Gaspere M, et al., 2008, WT1-specific T cell receptor gene therapy: Improving TCR function in transduced T cells, BLOOD CELLS MOLECULES AND DISEASES, Vol: 40, Pages: 113-116, ISSN: 1079-9796
Stauss HJ, Cesco-Gaspere M, Thomas S, et al., 2007, Monoclonal T-cell receptors: New reagents for cancer therapy, MOLECULAR THERAPY, Vol: 15, Pages: 1744-1750, ISSN: 1525-0016
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