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Background Why Epstein–Barr virus-related hemophagocytic lymphohistiocytosis (EBV-HLH) undergoes remission shortly after treatment and relapses rapidly and whether EBV infection in natural killer (NK)/T cells contributes to the deterioration of EBV-HLH are unknown. Methods EBV cell tropism and anti-EBV host cellular immunity were compared based on multicolor flow cytometry technique between EBV-HLH survivors and those who died to explore the key factors associated with the deterioration of HLH progression. Transcriptomics was performed to reveal the underlying mechanisms of EBV-HLH deterioration. Results In the deceased cases, EBV infection spread to NK (CD3-CD56+, 84.3%) and/or NKT (CD3 + CD56+, 67.9%) cells with a highly proliferating profile, whereas the infection was only limited to B cells in survivors. Although a similar low NK activation (Myc), proliferation (MKI67), and EBV LMP1-related carcinogenesis (TRAF2 and Jak3) genes. Conclusions Our study suggest that the oncogenicity of EBV-infected NK/NKT cells deteriorates EBV-HLH, and the spread of EBV to NK and NKT cells may indicate a prephase of NK/T lymphoma. Thus, the findings of this study may guide future therapeutic strategies for EBV-HLH.

The antitumor activity of NK cells in patients with chronic myeloid leukemia (CML) is inhibited by the leukemia microenvironment. Recent studies have identified that the expression of TIGIT, CD57, and KLRG1 is related to the function, maturation, and antitumor capabilities of NK cells. However, the characteristics of the expression of these genes in the peripheral blood (PB) and bone marrow (BM) from patients with CML remain unknown. In this study, we used multicolor flow cytometry to assay the quantity and phenotypic changes of NK cells in PB and BM from de novo CML (DN-CML) and CML patients acquiring molecular response (MR-CML). We found that the expression of TIGIT, which inhibits NK cell function, is increased on CD56+ and CD56dim NK cells in DN-CML PB compared with those in healthy individuals (HIs), and it is restored to normal in patients who achieve MR. We also found that the expression of CD57 on NK cells was approximately the same level in PB and BM from DN-CML patients, while decreased CD57 expression was found on CD56+ and CD56dim NK cells in HI BM compared with PB. Additionally, those two subsets were significantly increased in DN-CML BM compared to HI BM. The expression of CD57 correlates with replicative senescence and maturity for human NK cells; therefore, the increase in TIGIT on PB NK cells together with an increase in CD57 on BM NK cells may explain the subdued NK cell antileukemia capacity and proliferative ability in DN-CML patients. These results indicate that reversing the immune suppression of PB NK cells by blocking TIGIT while improving the proliferation of BM NK cells via targeting CD57 may be more effective in removing tumor cells.

Double-expressor diffuse large B-cell lymphoma (DLBCL) with17pdeletion is an aggressive and refractory disease. Immune checkpoint blockade and epigenetic drugs have been widely used, but the efficacy of different combined applications varied. We report a case with “double-expressor” DLBCL treated with a combined regimen which consisted of programmed cell death protein 1 (PD-1) inhibitor, DNA methyltransferase inhibitor (DNMTi), and histone deacetylase inhibitor (HDACi). A 50-year-old man presented with a 6-month history of hoarseness, and 10 days of progressive shortness of breath was diagnosed of DLBCL, stage IV. The patient failed to respond to the 1stline (R-EPOCH: rituximab, etoposide, vincristine, cyclophosphamide, doxorubicin, and dexamethasone), 2ndline (R-EPOCH + lenalidomide + ibrutinib), and a 3rdline chemotherapy combined with PD-1 inhibitor (sintilimab), decitabine, and GDP (gemcitabine, DDP, and dexamethasone). Surprisingly, patient’s condition was improved after treatment with PD-1 inhibitor in combination with DNMTi/HDACi. Restaging PET revealed dramatically radiological response.

Previous studies have reported that regulatory T cells (Tregs), which are physiologically engaged in the maintenance of immunological self-tolerance, have a critical role in the regulation of the antitumor immune response. Targeting Tregs has the potential to augment cancer vaccine approaches. The current study therefore aimed to evaluate the role of cytokine-induced killer (CIK) cell infusion in modulating Tregs in patients with non-small cell lung cancer (NSCLC). A total of 15 patients with advanced NSCLC were treated by an infusion of CIK cells derived from autologous peripheral blood mononuclear cells (PBMCs). By using flow cytometry and liquid chip analysis, subsets of T cells and natural killer (NK) cells in peripheral blood, and plasma cytokine profiles in the treated patients, were analyzed at 2 and 4 weeks after CIK cell infusion. Cytotoxicity of PBMCs (n=15) and NK cells (n=6) isolated from NSCLC patients was evaluated before and after CIK cell therapy. Progression-free survival (PFS) and overall survival (OS) were also assessed. Analysis of the immune cell populations before and after treatment showed a significant increase in NK cells (P

A new type of drug delivery system (DDS) based on single-walled carbon nanotubes (SWNTs) for controlled-release of the anti-cancer drug Paclitaxel (PTX) was constructed in this study. Chitosan (CHI) was non-covalently attached to the SWNTs to improve biocompatibility. Biocompatible hyaluronan was also combined to the outer CHI layer to realise the specific targeting property. The results showed that the release of PTX was pH-triggered and was better at lower pH (pH5.5). The modified SWNTs showed a significant improvement in intracellular reactive oxygen species (ROS), which may have enhanced mitogen-activated protein kinase activation and further promoted cell apoptosis. The results of western blotting indicated that the apoptosis-related proteins were abundantly expressed in A549 cells. Lactate dehydrogenase (LDH) release assay and cell viability assay demonstrated that PTX-loaded SWNTs could destroy cell membrane integrity, thus inducing lower cell viability of the A549 cells. Thus, this targeting DDS could effectively inhibit cell proliferation and kill A549 cells, is a promising system for cancer therapy.

Special AT-rich sequence-binding protein-1 (SATB1) is critical for genome organizer that reprograms chromatin organization and transcription profiles, and associated with tumor growth and metastasis in several cancer types. Many studies suggest that SATB1 overexpression is an indicator of poor prognosis in various cancers, such as breast cancer, malignant cutaneous melanoma, and liver cancer. However, their expression patterns and function values for adult T cell leukemia (ATL) are still largely unknown. The aim of this study is to examine the levels of SATB1 in ATL and to explore its function and mechanisms in Jurkat cell line. Here, we reported that SATB1 expressions were decreased in ATL cells (p

Background: Phosphofructokinase (PFK), a key enzyme of the glycolytic pathway, has L (liver), M (muscle), and P (platelet) isoforms with different tissue distributions. The Platelet Isoform of PFK (PFKP) plays an important role in regulating aerobic glycolysis and macromolecular biosynthesis to support cell growth. Up-regulation of PFKP is associated with progression and metastasis of varied kinds of solid organ tumor. However, less is known about the association between PFKP and hematology malignancy. Here, we investigated the role of PFKP in acute myeloid leukemia (AML). Methods: To characterize PFKP mRNA expression in AML, we performed qRT-PCR on bone marrow cells (BMCs) from 55 newly diagnosed AML patients with the median age of 47 years (range 16-82 years). The FAB type is M0 (2/55), M1 (3/55), M2 (15/55), M3 (11/55), M4 (11/55) and M5 (11/55). Two patients were diagnosed with myelodysplastic syndromes related AML. We screened for mutations in a selected panel of genes (NPM1, CEPBA, FLT3, KIT, WT1 and TP53), based on which patients were further categorized into standard (19/55), intermediate (21/55) and poor (15/55) cytogenetic risk groups. Patients were categorized into PFKPhigh and PFKPlow groups according to the median mRNA expression of PFKP. Complete remission (CR) rate was compared between two groups after 1 cycle and 4 cycles of chemotherapy. One year-relapse rate, overall survival rate (OS) and disease free survival rate (DFS) was also compared between PFKPhigh and PFKPlow groups. Results: PFKP mRNA expression of AML patients was significantly higher than that of the normal control (P Conclusions: PFKP expressions were increased in AML especially patients in poor cytogenetic risk group. PFKP might be a prognostic factor of poor clinical outcome of AML. Disclosures No relevant conflicts of interest to declare.

Objective To evaluate the treatment outcomes of hematopoietic stem cell transplantation (HSCT) in patients with T-cell lymphom / leukemia (TCL),observe hematopoietic reconstitution and transplant-related complications. Methods Seventeen TCL patients received HSCT from 2005 to 2013 in our hospital were retrospectively analyzed.Of the 17 patients,6 were T lymphoblastic lymphoma / leukemia (T-LBL),3 were Peripheral T-cell lymphoma / leukemia (PTL),2 were Anaplastic large cell lymphoma (ALCL),2 were Extranodal NK / T-cell lymphoma (NK / TCL),1 were Angioimmunoblastic T-cell lymphoma (ATCL) and 3 were Acute T lymphoblastic leukemia (T-ALL) with a median age of 35(19~67) years old.Ratio of male to female is 13F4. The distribution of stages was 2(14.2%),0(0%)and 12(85.7%) patients with stages II,III,and IV,respectively. The distribution according to international prognostic index (IPI) was 8(57.1%) patients in 2 score,1(7.1%) in 3 scores and 5 (35.7%) in 4 scores. Results ‡@17 patients were successfully engrafted, the median time of absolute neutrophil count(ANC) > 0.5×109/L was 11(8~15) days, the median time of platelet > 20×109/L was 13(8~18) days. 3 cases developed I degree acute GVHD, all patients were improved after treatment. ‡AAt a median follow-up of 36 (range,12-96) months,12 patients were alive and 5 relapsed and died from TCL after ASCT. The estimated 5-year probability of DFS and OS was (72.1±15.2)% and (59.7±15.2)% for all the patients. Conclusion The results showed that HSCT may significantly improve long-term outcome for patients with T-cell lymphoma / leukemia (TCL). Disclosures No relevant conflicts of interest to declare.

Background There is limited information on a special subtype of Acute myeloid leukemia (AML) characterized by >20% myeloblasts and >20% abnormal promyelocytes in bone marrow and peripheral blood. Objective The objective of the present investigation was to explore the clinical and laboratory features of seven patients with AML-M2/M3. Method We retrospectively assessed cell morphology, cytochemistry, immunophenotype, cytogenetics, and clinical features of seven patients with this rare subtype of AML. Results All seven cases had thrombocytopenia, coagulation abnormalities, >20% myeloblasts and abnormal promyelocytes. The PML/RARα fusion gene was present in six patients and two patients presented a mixed PML/RARα and AML1/ETO genotype. Five cases achieved CR and two cases did not achieve remission and one case transform into AML-M2 after CR1. Conclusions The clinical and laboratory features of seven patients with AML-M2/M3 are demonstrated in the present study, providing information on the FAB sub-classification.