Objective: To explore the expression of SLAMF6 on CD8(+) T cells in patients with severe aplastic anemia (SAA) and its correlation with disease immune status. Methods: By flow cytometry (FCM), SLAMF6 expression level in peripheral blood CD8(+) T cells was detected in 21 patients with SAA and 15 normal controls respectively from February 2017 to April 2018. The correlation between SLAMF6 expression level and hematopoietic functions, including HGB, PLT, the neutrophil granulocyte and reticulocyte absolute value in peripheral blood, hyperplasia degree (percentage of granulocytes, erythrocytes, lymphocytes and megakaryocytes in bone marrow) and perforin, granzyme B, IFN-γ expression level in CD8(+) T cells were evaluated. To further confirm the effect of SLAMF6 on CD8(+) T cells, anti-SLAMF6 Ab was used to block SLAMF6 pathway (IgG as control), and FCM was used to detect the perforin, granzyme B, and IFN-γ production of CD8(+) T cells. Results: The expression of SLAMF6 on CD8(+) T cells in untreated SAA patients[(56.29±12.97)%]was significantly lower than that of normal controls[(80.96±7.36)%](t=-7.672, P<0.001). The expression of SLAMF6 on CD8(+) T cells in SAA patients were positively correlated with the HGB, PLT, the neutrophil granulocyte and reticulocyte absolute value in peripheral blood, percentage of granulocytes, erythrocytes in bone marrow (all P<0.05), but they were negatively correlated with the percentage of lymphocytes in bone marrow, and the expression of perforin, granzyme B, and IFN-γ of CD8(+) T cells (all P<0.05). After blocking SLAMF6 pathway by anti-SLAMF6 Ab, the expression levels of perforin, granzyme B and IFN-γ in SAA patients were significantly higher than those in the untreated group, and the differences were statistically significant (all P<0.05). Conclusions: SLAMF6 is significantly down-regulated on CD8(+) T cells in SAA patients, which may act as a negative immunoregulatory molecule participating in the mechanism of SAA by affecting the functional molecules secretion on CD8(+) T cells.
Anemia, Aplastic ; Bone Marrow ; CD8-Positive T-Lymphocytes ; Flow Cytometry ; Humans ; Perforin ; Signaling Lymphocytic Activation Molecule Family

BACKGROUNDThe SLAM family recently has been reported to show an important biological role in lymphocyte development and immunological function, and it is efficient to highly purify hematopoietic stem cells using a simple combination of SLAM family members. To elucidate the presence of this family on acute lymphoblastic leukemia (ALL), as well as its relationship with the leukemia-initiating potential, we analyzed the expression pattern of this family members on human ALL progenitor cells, combined with serial xenotransplantation assay.

METHODSExpression analysis was carried out by flow cytometry. We combined the expression pattern of human CD(150), CD(244) and CD(48) with serial xenotransplantation of B-ALL progenitor cells to indicate their relationship.

RESULTSCD(48) and CD(244) were expressed on most B-ALL progenitor cells, the percentage being (93.08 ± 6.46)% and (63.37 ± 29.31)%, respectively. Interestingly, the proportion of CD(150)(+) cells declined obviously in engrafted cases ((24.94 ± 7.32)%) compared with non-engrafted cases ((77.54 ± 5.93)%, P < 0.01), which indicated that only blast cells with low percentage of CD(150)(+) population were able to reconstitute leukemia into primary, secondary and tertiary NOD/SCID mice.

CONCLUSIONSSLAM family members are present on B-ALL progenitor cells and the leukemia-initiating potential of leukemic blasts is correlated negatively with the proportion of CD(150)(+) cells, the percentage of which can serve as a useful predictor for engraftment success of B-ALL to immune deficient mice.

Adolescent ; Adult ; Aged ; Animals ; Antigens, CD ; analysis ; CD48 Antigen ; Child, Preschool ; Female ; Flow Cytometry ; Humans ; Infant ; Male ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; blood ; Receptors, Cell Surface ; analysis ; Receptors, Immunologic ; analysis ; Signaling Lymphocytic Activation Molecule Family ; Signaling Lymphocytic Activation Molecule Family Member 1 ; Transplantation, Heterologous

Measles virus is an enveloped virus with a non-segmented negative-sense RNA genome. Two envelope glycoproteins on the viral surface, namely hemagglutinin (H) and membrane fusion protein (F), are responsible for the virus entry into susceptible host cells. The specific interaction between H and its cellular receptors is a key step in successful virus infection, determining the infectivity and tissue tropism of the measles virus. Thus far, three H receptors have been identified, including the complement regulatory molecule CD46, the signaling lymphocyte activation molecule (SLAM) and the cell adhesion molecule Nectin-4. Here, we reviewed our molecular understanding on the recognition mechanism of these receptors by the viral H protein, aiming to promote future studies on antiviral drug design and measles virus-based oncolytic therapy.
Animals ; Antigens, CD ; metabolism ; Cell Adhesion Molecules ; metabolism ; Hemagglutinins, Viral ; metabolism ; Humans ; Measles virus ; pathogenicity ; physiology ; Membrane Cofactor Protein ; metabolism ; Membrane Fusion ; Membrane Fusion Proteins ; metabolism ; Receptors, Cell Surface ; metabolism ; Receptors, Virus ; metabolism ; Signaling Lymphocytic Activation Molecule Family Member 1

Multiple myeloma (MM), considered an incurable hematological malignancy, is characterized by its clonal evolution of malignant plasma cells. Although the application of autologous stem cell transplantation (ASCT) and the introduction of novel agents such as immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have doubled the median overall survival to eight years, relapsed and refractory diseases are still frequent events in the course of MM. To achieve a durable and deep remission, immunotherapy modalities have been developed for relapsed/refractory multiple myeloma (RRMM). Among these approaches, chimeric antigen receptor (CAR) T-cell therapy is the most promising star, based on the results of previous success in B-cell neoplasms. In this immunotherapy, autologous T cells are engineered to express an artificial receptor which targets a tumor-associated antigen and initiates the T-cell killing procedure. Tisagenlecleucel and Axicabtagene, targeting the CD19 antigen, are the two pacesetters of CAR T-cell products. They were approved by the US Food and Drug Administration (FDA) in 2017 for the treatment of acute lymphocytic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). Their development enabled unparalleled efficacy in combating hematopoietic neoplasms. In this review article, we summarize six promising candidate antigens in MM that can be targeted by CARs and discuss some noteworthy studies of the safety profile of current CAR T-cell therapy.
ADP-ribosyl Cyclase 1/immunology* ; B-Cell Maturation Antigen/immunology* ; Humans ; Immunotherapy, Adoptive/methods* ; Multiple Myeloma/therapy* ; Receptors, Chimeric Antigen/immunology* ; Receptors, G-Protein-Coupled/immunology* ; Signaling Lymphocytic Activation Molecule Family/immunology* ; Syndecan-1/immunology* ; T-Lymphocytes/immunology*