The interaction between Tim-3 on T cell and its ligand, Galectin-9, negatively regulates cellular immune responses. However, the role of Tim-3/Galectin-9 pathway in the immune evasion of cervical cancer remains unknown. This study is to investigate the expression, function, and regulation of Tim-3/Galectin-9 signaling pathway in human papilloma virus (HPV) positive cervical cancer. Flow cytometry showed that Tim-3 expression on T cell and Galectin-9 expression on monocytes in HPV positive cervical cancer patients were significantly higher compared to cervical intraepithelial neoplasia and benign uterine fibroids Tim-3 + CD4+ Th1 cells and Tim-3 + CD8+ T cells in HPV positive cervical cancer patients were significantly reduced after surgery. Serum TGF-β and IL-10 levels were positively correlated with Tim-3 + Treg cells, while IFN-γ and IL-2 were negatively correlated with Tim-3 + Th1 cells. Additionally, Tim-3 + CD4+ T cells were positively correlated with Galectin-9 + monocytes. Survival curve analysis showed that Tim-3 + CD4+ T cells were negatively correlated with patient survival, and closely related to FIGO stage, degree of differentiation, and lymph node metastasis of HPV positive cervical cancer. In vitro experiments showed that by blocking the Tim-3/Galectin-9 pathway, the proliferation of T cells and their ability to express IFN-γ, IL-2, perforin, and granzyme B was significantly restored. In conclusion, high levels of Tim-3 and Galectin-9 in HPV positive cervical cancer patients play roles in the progression of disease by promoting Treg cells to inhibit the cytotoxic function of Th1 and CD8+ T cells. Tim-3/Galectin-9 may serve as a new immunotherapy target for patients with HPV positive cervical cancer.
The present study is to measure the expression of programmed death (PD)-1 / programmed death ligand-1 (PD-L1) negative costimulatory molecules, soluble format sPD-1 in patients with immune thrombocytopenia (ITP), and to investigate their correlation with the secretion of cytokines. A total of 35 patients with ITP were included in the present study. Twenty healthy subjects who received physical examination at our hospital were included as control group. Peripheral blood was collected from all ITP patients and healthy subjects. Flow cytometry was performed to determine the percentages of PD-1
Related HLA-haploidentical HSCT has been applied more and more recently, but the reconstitution of T lymphocyte subsets and its clinical significance in patients received related HLA-haploidentical non T-cell depleted in vitro high-dose peripheral blood hematopoietic SCT (RHNT-PSCT) are incompletely defined. In the present study of our RHNT-PSCT, we found that in non-aGVHD group, CD3(+) T lymphocyte recovered to normal levels gradually between 60 and 90 days, and the recovery of CD4(+) T lymphocyte was retarded significantly, CD4(+)/CD8(+) ratio was apparently inverted. Whereas, the ratio of CD4(+) CD25(+) Foxp3(+) Treg cells was significantly lower in aGVHD group than in healthy control group and non-aGVHD group, and also in grade III-IV aGVHD patients than in grade I-II aGVHD patients. Meanwhile, we observed the level of interleukin-10 (IL-10) gradually increased in serum of patients without aGVHD, but decreased in III-IV aGVHD patients significantly. Spearman correlation analysis showed that serum IL-10 level was negatively correlated with the grade of aGVHD. These results suggest that the reconstitution of peripheral blood T lymphocyte subsets is good, and dynamic detection of Treg cells and serum IL-10 level might predict aGVHD in the early stage after our RHNT-PSCT.
CD8+ T cells can participate in immune action by secreting various cytokines, which have a killing effect on certain viruses, tumor cells, and other antigenic substances. However, in studies such as chronic viral infections and some parasitic infections, CD8+ T lymphocyte showed functional depletion, and its immune dysfunction was an important reason for the persistence of infection. Tim-3 has been shown to be a negative regulator of CD8+ T cell function, causing depletion of CD8+ T cells in cancer and chronic infection. However, the relationship between Tim-3 and CD8+ T cells in Echinococcus multilocularis infection is not clear.In this study, we analyzed peripheral blood CD8+ T cells from 62 alveolar echinococcosis (AE) patients and 30 healthy controls.Compared with the healthy control group, the proportion of CD8+ T cells in the peripheral blood of AE patients increased significantly, while the levels of perforin, granzyme B and IFN-γ in peripheral blood CD8+ T cell related factors of metabolically active alveolar echinococcosis (MAAE) patients decreased significantly. Later detection revealed that the expression of Tim-3 on CD8+ T cells in the peripheral blood of MAAE patients was significantly higher than that of metabolically inactive alveolar echinococcosis (MIAE) patients and healthy controls. The expression levels of function-related factors perforin, granzyme B and IFN-γ in CD8+ Tim-3+ T cell were significantly lower in the CD8+Tim-3- T cells of AE patients. In vitro, the secretion of CD8+ T cell-associated factors was significantly restored by inhibiting Tim-3 expression.Therefore, the depletion of CD8+ T lymphocyte in patients with alveolar echinococcosis disease is considered to be related to the high expression of Tim-3 on the surface.
The present study was designed to investigate the effect of adipose‑derived stem cells (ADSCs) on acute graft vs. host disease (aGVHD) and hematopoietic recovery after allogeneic hematopoietic stem cell transplantation. ADSCs, bone marrow‑derived stem cells (BMSCs) and fibroblasts were cultured. ADSCs were cocultured with hematopoietic stem/progenitor cells. Then, ADSCs were infused into the aGVHD rat model. The survival of the rats was recorded. Livers and small intestines were obtained from sacrificed rats for pathological examinations. Expression of the Sry gene in recipient rats that survived longer than 21 days was examined by real‑time PCR to detect the presence of donor Y chromosome. Expression of serum interferon (INF)‑γ and interleukin (IL)‑4 was detected by ELISA at 0, 7, 14, 21 and 50 days after transplantation. Transplantation of ADSCs improved the survival of aGVHD rats. Survived ADSCs participated in hematopoietic reconstitution in aGVHD rats. ADSCs decreased aGVHD severity by immunomodulation. ADSCs support the proliferation of hematopoietic stem/progenitor cells in vitro. The present study demonstrated that ADSCs may reduce aGVHD by influencing the balance of IL‑4 and INF‑γ and can promote long‑term hematopoiesis.
Abstract Background Galectin‐9 and myeloid‐derived suppressor cells (MDSCs) have an important role in tumors, but their clinical values in chronic lymphocytic leukemia (CLL) have not been fully elucidated. This study aimed to analyze the prognosis values of Galectin‐9 and MDSCs in CLL. Methods The concentrations of Galectin‐9, argininase‐1, and inducible nitric oxide synthase in serum were detected by enzyme‐linked immune sorbent assay. The expression of Tim‐3 protein in peripheral blood mononuclear cell was detected by Western blot. Flow cytometry was used to analyze the percentages of Tim‐3 on T‐cells (CD3 + T, CD4 + T, and CD8 + T cells) and MDSCs. Results Our results showed that Galectin‐9 and MDSCs significantly increased in CLL patients and were closely related to the disease progression. Patient's receiver operating characteristic, progression‐free survival, and Cox regression analysis showed that Galectin9 and MDSCs were poor prognostic factors of CLL. Conclusion Galectin‐9 and MDSCs were associated with clinical progression and could be important prognostic indicators for CLL.
To explore the application of immunophenotype resources in clinical teaching of hematologic malignancies. There were 102 students who studied the content of hematologic malignancies were divided into experimental group and control group. The experimental group introduced immunophenotype resources to assist teaching. The control group used traditional teaching mode, then we observed the teaching effects of the two groups. The scores of the examinations in the experimental group were significantly higher than those in the control group (P<0.05). The learning drives, deep learning, learning control and strong learning scores of experimental group were significantly higher than the control group (P<0.05). The introduction of immunophenotype resources in the teaching of hematological malignancies can improve the quality of teaching and the initiative of students.
The present study is to measure the expression of programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1), as well as its clinical significance in cervical cancer patients. Our results showed that different T cell subsets in patients with cervical cancer had high expression of PD-1, and DCs had high expression of PD-L1. High expression of PD-1 on Treg cells in cervical cancer patients facilitated the production of TGF-β and IL-10 but inhibited the production of IFN-γ. Cervical cancer elevated the expression of PD-1 and PD-L1 in mRNA level. PD-1 expression in peripheral blood of cervical cancer patients was related with tumor differentiation, lymph node metastasis, and invasiveness. PD-1/PD-L1 pathway inhibited lymphocyte proliferation but enhanced the secretion of IL-10 and TGF-β in vitro. In summary, our findings demonstrate that elevated levels of PD-1/PD-L1, TGF-β, and IL-10 in peripheral blood of cervical cancer patients may negatively regulate immune response against cervical cancer cells and contribute to the progression of cervical cancer. Therefore, PD-1/PD-L1 pathway may become an immunotherapy target in the future.
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