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Simple Summary: Plasmacytoid dendritic cells are the main type I interferon producing cells in humans and are able to modulate innate and adaptive immune responses. Tumor infiltration by plasmacytoid dendritic cells is already described and is associated with poor outcomes in cancers. In hematological diseases, Blastic Plasmacytoid Dendritic Cells Neoplasm (blastic counterpart) is well described, but little is known about tumor infiltration by mature plasmacytoid dendritic cells described in Myeloid Neoplasms (myeloid tumor cells and clonal pDC proliferation). This review provides a comprehensive overview of plasmacytoid dendritic cells in Myeloid Neoplasms. Plasmacytoid dendritic cells (pDC) are the main type I interferon producing cells in humans and are able to modulate innate and adaptive immune responses. Tumor infiltration by plasmacytoid dendritic cells is already well described and is associated with poor outcomes in cancers due to the tolerogenic activity of pDC. In hematological diseases, Blastic Plasmacytoid Dendritic Cells Neoplasm (BPDCN), aggressive leukemia derived from pDCs, is well described, but little is known about tumor infiltration by mature pDC described in Myeloid Neoplasms (MN). Recently, mature pDC proliferation (MPDCP) has been described as a differential diagnosis of BPDCN associated with acute myeloid leukemia (pDC-AML), myelodysplastic syndrome (pDC-MDS) and chronic myelomonocytic leukemia (pDC-CMML). Tumor cells are myeloid blasts and/or mature myeloid cells from related myeloid disorders and pDC derived from a clonal proliferation. The poor prognosis associated with MPDCP requires a better understanding of pDC biology, MN oncogenesis and immune response. This review provides a comprehensive overview about the biological aspects of pDCs, the description of pDC proliferation in MN, and an insight into putative therapies in pDC-AML regarding personalized medicine. [ABSTRACT FROM AUTHOR]

Production of functional plasmacytoid dendritic cells - targeted chimeric antigen receptor T cells from patients with immune-mediated inflammatory diseases After 15 days of culture, CAR123 expression was stable in both cases (Figure 1a) and CAR123 maintained a good proliferation rate: 244.3 ± 201.4% for patients ( I n i = 23) and 571.6 ± 294.5% for HD ( I n i = 5) ( I P i = 0.0052) (Figure 1b). Https://doi.org/10.1093/bjd/ljad105 Dear Editor, Mainly developed in the field of oncology, chimeric antigen receptor T-cell (CAR-T cell) therapy has been extended more recently to other areas such as infectious diseases, cardiac fibrosis or autoimmune diseases (AIDs).[1] Patients with refractory systemic lupus erythematosus (SLE) treated with CD19-targeted CAR-T cells demonstrated an improvement of clinical symptoms and normalization of laboratory parameters including seroconversion of anti-double-stranded DNA antibodies along with a deep depletion of B cells.[2] Increasing evidence suggests that plasmacytoid dendritic cells (pDCs) are involved in the development of different pDC-driven AIDs and immune-mediated inflammatory diseases (IMIDs), especially through the overproduction of proinflammatory cytokines such as type 1 interferons.[3] It is thus conceivable that elimination of pDCs might be beneficial to improve AID and IMID evolution as was recently demonstrated in a phase II trial involving patients with SLE treated with an antibody-binding of blood dendritic cell antigen 2 (BDCA2).[4] To the best of our knowledge, no CD123-targeted CAR-T cells (CAR123) have yet been developed for AID and IMID treatment. [Extracted from the article]

Background: Cryopreservation of ovarian tissue is a fertility-preservation option for women before gonadotoxic treatments. However, cryopreserved ovarian tissue transplantation must be performed with caution in women with malignancies that may metastasize to the ovaries. For this purpose, detecting minimal residual disease (MRD) in the ovarian cortex using sensitive methods is a crucial step. We developed an automated ovarian tissue dissociation method to obtain ovarian cell suspensions. Results: We assessed MRD by multicolor flow cytometry (MFC) in cryopreserved ovarian cortex of 15 leukemia patients: 6 with B-cell acute lymphoblastic leukemia (B-ALL), 2 with T-cell acute lymphoblastic leukemia (T-ALL) and 7 with acute myeloid leukemia (AML). Ovarian MRD was positive in 5 of the 15 leukemia patients (one T-ALL and 4 AML). No B-ALL patient was positive by MFC. Quantitative reverse-transcribed polymerase chain reaction was performed when a molecular marker was available, and confirmed the MFC results for 3 patients tested. Xenografts into immunodeficient mice were also performed with ovarian cortical tissue from 10 leukemia patients, with no evidence of leukemic cells after the 6-month grafting period. Conclusions: In conclusion, this is the first study using MFC to detect MRD in ovarian cortical tissue from acute leukemia patients. MFC has been accepted in clinical practice for its ease of use, the large number of parameters available simultaneously, and high throughput analysis. We demonstrate here that MFC is a reliable method to detect MRD in cryopreserved ovarian tissue, with a view to controlling the oncological risk before ovarian tissue transplantation in leukemia patients. [ABSTRACT FROM AUTHOR]

Simple Summary: We used fresh or thawed Umbilical Cord Blood (UCB) to produce CAR-T cells directed against CD123, and we compared their functionality to Peripheral Blood (PB) CAR-T cells. T cells expressing CD123 CAR, derived from UCB, was exhibited through a high transduction rate, activation status, and cytotoxic potential in vitro as PB derived CAR-T cells. Moreover, we obtained T cells that had a less differentiated profile than the PB-derived T cells. UCB derived CAR-T can significantly control tumor progression in mice models. CAR-T obtained from thawed or fresh UCB gives the same results. Chimeric Antigen Receptor (CAR) therapy has led to great successes in patients with leukemia and lymphoma. Umbilical Cord Blood (UCB), stored in UCB banks, is an attractive source of T cells for CAR-T production. We used a third generation CD123 CAR-T (CD28/4-1BB), which was previously developed using an adult's Peripheral Blood (PB), to test the ability of obtaining CD123 CAR-T from fresh or cryopreserved UCB. We obtained a cell product with a high and stable transduction efficacy, and a poorly differentiated phenotype of CAR-T cells, while retaining high cytotoxic functions in vitro and in vivo. Moreover, CAR-T produced from cryopreserved UCB are as functional as CAR-T produced from fresh UCB. Overall, these data pave the way for the clinical development of UCB-derived CAR-T. UCB CAR-T could be transferred in an autologous manner (after an UCB transplant) to reduce post-transplant relapses, or in an allogeneic setting, thanks to fewer HLA restrictions which ease the requirements for a match between the donor and recipient. [ABSTRACT FROM AUTHOR]

Background: Cryopreservation of ovarian tissue is a fertility-preservation option for women before gonadotoxic treatments. However, cryopreserved ovarian tissue transplantation must be performed with caution in women with malignancies that may metastasize to the ovaries. For this purpose, detecting minimal residual disease (MRD) in the ovarian cortex using sensitive methods is a crucial step. We developed an automated ovarian tissue dissociation method to obtain ovarian cell suspensions. Results: We assessed MRD by multicolor flow cytometry (MFC) in cryopreserved ovarian cortex of 15 leukemia patients: 6 with B-cell acute lymphoblastic leukemia (B-ALL), 2 with T-cell acute lymphoblastic leukemia (T-ALL) and 7 with acute myeloid leukemia (AML). Ovarian MRD was positive in 5 of the 15 leukemia patients (one T-ALL and 4 AML). No B-ALL patient was positive by MFC. Quantitative reverse-transcribed polymerase chain reaction was performed when a molecular marker was available, and confirmed the MFC results for 3 patients tested. Xenografts into immunodeficient mice were also performed with ovarian cortical tissue from 10 leukemia patients, with no evidence of leukemic cells after the 6-month grafting period. Conclusions: In conclusion, this is the first study using MFC to detect MRD in ovarian cortical tissue from acute leukemia patients. MFC has been accepted in clinical practice for its ease of use, the large number of parameters available simultaneously, and high throughput analysis. We demonstrate here that MFC is a reliable method to detect MRD in cryopreserved ovarian tissue, with a view to controlling the oncological risk before ovarian tissue transplantation in leukemia patients. [ABSTRACT FROM AUTHOR]

1 Pre-treatment TEP SCAN (a) and after 3 months of treatment (b) A PET scan was performed after the third cycle of association showing a complete metabolic remission (Fig. 1:CAS:528:DC%2BD1MXmvFyjur0%3D. 10.1111/j.1365-2141.2009.07679.x 2 Garnache-Ottou F, Vidal C, Biichlé S, Renosi F, Poret E, Pagadoy M. How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients? Recent papers [[6]-[8]] showed that venetoclax combined with decitabine or 5-Aza in treatment-naive elderly patients with AML was effective and well tolerated, leading this association to become a standard of treatment in this indication. [Extracted from the article]