【Abstract】Objective The effects of tumor infiltrating lymphocytes (TIL) on cellular immunologic function of patients with breast cancer were studied. Methods Twenty five patients with breast cancer were treated by the TIL that were isolated from tissue of tumor. T cell subgroups and natural killer cell (NK cell) activity of peripheral blood, the levels of serum soluble interleukin-2 receptor (sIL-2R) were assayed before and after treatment. Results CD3, CD4, CD4/CD8 and NK cell activity were ascended obviously, and CD8, sIL-2R were descended obviously after the treatment of TIL. Conclusion TIL can enhance the cellular immunologic function of patients with breast cancer.
Objective To investigate the role of T cell factor-4 (TCF-4) in the carcinogenesis of colorectal cancer. Methods Relevant references about TCF-4 and the carcinogenesis of colorectal cancer, which were published recently domestic and abroad, were collected and reviewed. Results For TCF-4 gene, multiple isoforms are generated by way of alternative splicing, which encode different proteins. TCF-4 protein is sequence-specific DNA binding protein and is incapable of activating or repressing transcription independently, but it can interact with distinct partners to lead to different effects through multiple domains. Conclusion TCF-4 might be viewed as nuclear vehicles targeting other auxiliary proteins to a specific set of promoters and functions as molecular switch during the carcinogenesis of colorectal cancer.
Regulatory T cells (Treg) are critical for regulation of tolerance, control immune responses to self-antigens thereby preventing autoimmunity, and limiting responses to foreign antigens thereby minimizing T cell-mediated immunopathology. Recent data indicate that suppression of organ-specific autoimmunity is dependent on the antigen specificity of Treg. An emerging model of Treg action is that organ-specific Treg acquire suppressive activity through activation by dendritic cells expressing specific antigens. Thus, the efficacy of Treg-based therapy should be increased by using antigen-specific Treg rather than polyclonal Treg. It is necessary to identify relevant antigens and to expand antigen-specific Treg from polyclonal populations. Here, we discuss recent techniques for expansion of antigen-specific Treg, function and antigen specificity of Treg and the therapeutic potential of Treg in controlling autoimmune disease and inducing transplant tolerance.
Objective To investigate the efficacy of continuous blood purification ( CBP) in the treatment of severe sepsis, and explore the related immune regulatory mechanisms. Methods Forty-eight patients with severe sepsis were randomly divided into a control group ( n =23) and a CBP group ( n =25) .CD4 + CD25 + regulatory T cells ( Treg% ) in peripheral blood and APACHEⅡ score were measured dynamically before treatment and 12, 24, 36, 48, 60, 72 hours after treatment. Meanwhile the length of ICUstay, duration of mechanical ventilation, and 28 day mortality were determined. Results Compared with the control group, the length of ICU stay, ventilator time, incidence of multiple organ failure, and mortality decreased significantly in the CBP group ( P lt; 0. 05) . And CBP also decreased Treg% and APACHEⅡ score significantly. There was a positive correlation between Treg% and APACHEⅡ score ( r =0. 804, P lt;0. 01) .Conclusion Early CBP treatment can reduce Treg%, improve cellular immunity and improve the prognosis of sepsis.
Objective To investigate the possibility of enhancing the inducing rate of adipose-derived stem cells (ASCs) into epidermal cells in the medium containing all-trans retinoic acid (ATRA) by supplementing with HaCaT condition medium. Methods ASCs were isolated and identified by detecting the expression of CD34, CD45, CD73, CD90, and CD105 with flow cytometry and differentiating into adipose and osteoblast lineage in the induction medium. The air-liquid interface cell culture model was established with the Transwell Room. The induction medium A contained ATRA, epidermal growth factor (EGF), and keratinocyte growth factor (KGF), while the induction medium B contained ATRA, EGF, KGF, and HaCaT condition medium. Experiment was divided into three groups cultured for 12 days: induction medium A (group A), induction medium B (group B), basic medium (group C). The epidermal cell surface markers: cytokeratin (CK) 14, 15, 16, 19 (Pan-CK) were detected by flow cytometry and CK14 were identified by immunofluorescence stain. Results After induction for 12 days, flow cytometry showed that the positive rate of Pan-CK in group B [(22.0±3.5)%] was higher than that in group A [(11.9±2.7)%], which were both higher than that in group C [(1.1±0.3)%], and the differences were statistical significantly (P<0.01). Immunofluorescence stain showed that the positive rate of CK14 in group B was higher than that in group A [(19.5±7.0)%vs. (10.8±5.7)%, P<0.01], and the expression of CK14 was negative in group C. Conclusion HaCaT condition medium can enhance the ability of ASCs differentiation into epidermal cells in the culture medium containing ATRA.
ObjectiveTo investigate the expression of CD4+CD25highCD127lowTreg (Treg) and related cytokines in peripheral blood of COPD patients with pulmonary hypertension and explore its clinical significance. MethodsPeripheral blood lymphocytes and serum were collected from 65 COPD patients with chronic pulmonary hypertension (the CPH group) and 20 COPD patients with normal pulmonary artery pressure (the control group). Flow cytometry was used to detect the Treg/CD4+ T cells and calculate its ratio, enzyme-linked immunosorbent assay was used to detect the serum contents of interleukin (IL)-6,IL-10 and tumor necrosis factor α (TNF-α). ResultsTreg can be detected in the peripheral blood of patients of COPD with or without PH, however, the Treg ratio in the CPH group was significantly lower than that in the control group [(7.41±1.12)% vs. (9.04±2.11)%, P<0.05]. Compared with the control group, the IL-10 level was significantly lower [(4.47±0.88)pg/mL vs. (5.18±0.26)pg/mL], while IL-6and TNF-α contents were significantly higher in the CPH group [(7.49±0.95)pg/mL vs. (6.76±0.35)pg/mL, (28.61±9.16)pg/mL vs. (19.64±4.85)pg/mL, P<0.05]. There was a positive correlation between Treg ratio and serum IL-10 level (r=0.41, P<0.05), and negative correlation between Treg ratio and TNF-α or IL-6 contents (r=0.45 or 0.37,P<0.05). The Treg ratio of the patients with severe pulmonary hypertension was lower than that in the patients with mild pulmonary hypertension [(7.42±1.03)% vs. (10.47±2.55)%,P<0.05). ConclusionsContents of Treg and IL-10 decrease while IL-6 and TNF-α increase in peripheral blood of COPD patients with pulmonary hypertension. It suggests that Treg cells and related cytokines may involve in the pathogenesis and progression of CPH. Treg may becomea potential biological prognosis indicator and treatment target of CPH in the future.
ObjectivesTo systematically review the clinical response rate of CD19 chimeric antigen receptor modified-T cells (CD19CART) in the treatment of B cell hematological malignancies.MethodsPubMed, EMbase, CNKI, WanFang Data and VIP databases were searched to collect cohort studies about CD19CART in the treatment of B cell hematological malignancies from 2000 to 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, a single rate meta-analysis was performed by R software and SPSS 16.0 software.ResultsA total of 13 prospective cohort studies were included. The results of single group rate meta-analysis showed that the overall pooled response rate of CD19 CART was 68% (95%CI 0.51 to 0.82). The 6 months and 1-year PFS after CD19 CART infused by Kaplan-Meier were 46% (95%CI 0.35 to 0.56) and 24% (95%CI 0.16 to 0.34), respectively. The median duration was 180 days (95%CI 138 to 222). The COX regression model showed lymphodepletion to be the only influence factor of PFS.ConclusionsCD19 CART has a good clinical response rate in the treatment of B cell hematological malignancies. Lymphodepletion is the only important impact on the response rate and PFS. Due to limited quality and quantity of included studies, more high quality studies are required to verify the above conclusions.
ObjectiveTo improve clinicians' understanding of severe cytokine release syndrome (CRS) through reporting the clinical manifestation, diagnosis, treatment, and prognosis of CRS after chimeric antigen receptor T (CAR-T) cell therapy in a patient with solid tumor. Methods A patient with ovarian cancer who suffered severe CRS after CAR-T cell therapy in the Department of Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University was reviewed. Relevant studies were searched for literature review. Results The patient, a 55-year-old woman, was diagnosed with ovarian cancer in early 2016 and continued to progress despite multiple lines of treatment, so she received CAR-T cell therapy on September 16, 2022. The patient developed a fever 2 days after infusion, and developed dyspnea and shortness of breath with oxygen desaturation 2 days later. Her condition kept deteriorating with respiratory distress and severe hypoxia 6 days after infusion, and the level of interleukin-6 and interferon-gamma continued to be elevated. Chest CT showed pleural effusion and massive exudation of both lungs. Considered to have acute respiratory distress syndrome (ARDS) due to severe CRS, she was transferred to the intensive care unit (ICU). The patient was treated with tocilizumab, high-dose intravenous glucocorticoid pulses, mechanical ventilation, and sivelestat sodium for ARDS. Her symptoms were gradually relieved, and the results of laboratory tests were gradually stabilized. The patient was extubated 6 days after ICU admission and discharged from ICU a week later. Six patients were screened out with ARDS or acute respiratory failure caused by CRS after CAR-T cell therapy, whose treatments were mainly anticytokine agents combined with high-flow oxygen therapy or invasive mechanical ventilation. One of them died. ConclusionsClinicians should be alert to severe CRS during the administration of CAR-T cell. Rapid interruption of the inflammation development is the key to all treatments. If respiratory and/or circulatory dysfunction occurs, patients should be transferred to ICU in time for organ support therapy.
Objective To investigate the effects of ulinastatin on Treg/Th17 and immune status in patients with severe sepsis.Methods A total of 80 patients with severe sepsis, who were hospitalized in ICU during October 2011 to July 2012, were randomly divided into a routine group and a ulinastatin group. The patients in the ulinastatin group were intravenously administered 30mg ulinastatin three times per day for 5 days in addition to routine bundle treatment. The expression of Treg, Th17 and HLA-DR were detected on the first day in ICU and 5 days after treatment. 20 healthy individuals served as controls. Results Compared with the control group, the severe sepsis group had overexpression of Treg and Th17 ( P lt;0. 01) , higher ratio of Treg/Th17( P lt;0. 01) , and decreased HLA-DR expression of CD14 monocyte ( P lt; 0. 01) . In the severe sepsis patients, ulinastatin injection reduced the abnormal expression of Treg and Th17 ( P lt; 0. 01) , decreased the ratio of Treg/Th17( P lt; 0. 01) , and improved the expression of HLA-DR ( P lt; 0. 01) more effectively compared with the routine treatment. Ulinastatin also lowered 28-day mortality of the patients with sepsis, but the difference between the ulinastatin group and the routine group was not significant. Conclusions In severe sepsis patients, there were abnormal overexpression of Treg and Th17, imbalance of Treg/Th17, and underexpression of HLA-DR which imply an immune suppression. Ulinastatin can decrease the expression of Treg and Th17, inverses the ratio of Treg/Th17, and improve the expression of HLA-DR, so as to improve the prognosis of severe sepsis patients.
Objective To investigate the proportions of CD4+ T cells, CD8+ T cells, and mutant of p53 gene in the microenvironment of breast infiltrating ductal carcinoma, and to explore its’ correlation with prognosis of breast infiltrating ductal carcinoma. Methods Eighty-five cases of breast infiltrating ductal carcinoma were collected who underwent surgery in the 371st Central Hospital of Peoples’ Liberation Army from 2010 to 2012, and then detected the proportion of CD4+ T cells and CD8+ T cells, ratio of CD4+ T cells to CD8+ T cells, and mutant of p53 gene in the cancer tissues with immunohistochemistry. Comparison between the sentinel lymph node metastasis group and non-sentinel lymph node metastasis group, mutant of p53 gene group and non-mutant of p53 gene group on the proportions of CD4+ T cells, CD8+ T cells, and ratio of CD4+ T cells to CD8+ T cells were performed, as well as the relationship between proportion of CD8+ T cells/mutant of p53 gene and prognosis of breast infiltrating ductal carcinoma. Results ① The relationship between proportion of CD4+ T cells/proportion of CD8+ T cells/ratio of CD4+ T cells to CD8+ T cells and situation of sentinel lymph node metastasis: at cluster, compared with the sentinel lymph node metastasis group, the proportion of CD8+ T cells was lower in the non-sentinel lymph node metastasis group (P<0.05), but there was no significant difference on the proportion of CD4+ T cells and ratio of CD4+ T cells to CD8+ T cells (P>0.05); at stroma, compared with the sentinel lymph node metastasis group, the proportions of CD4+ T cells and CD8+ T cells were lower, but the ratio of CD4+ T cells to CD8+ T cells was higher in the non-sentinel lymph node metastasis group (P<0.05). ② The relationship between proportion of CD4+ T cells/proportion of CD8+ T cells/ratio of CD4+ T cells to CD8+ T cells and mutant of p53 gene: both at the cluster and stroma, compared with the mutant of p53 gene group, the proportions of CD4+ T cells and CD8+ T cells were lower, but the ratio of CD4+ T cells to CD8+ T cells was higher in the non-mutant of p53 gene group (P<0.05). ③ The relationship between proportion of CD8+ T cells/mutant of p53 gene and prognosis of breast infiltrating ductal carcinoma: the prognosis was worse in patients with high degree of infiltration of CD8+ T cells and mutant of p53 gene than those patients with low degree of infiltration of CD8+ T cells and non-mutant of p53 gene (P<0.05). Conclusions The proportions of CD4+ T cells and CD8+ T cells, and ratio of CD4+ T cells to CD8+ T cells are associated with the situation of sentinel lymph node metastasis and mutant of p53 gene, and the degree of infiltration of CD8+ T cells and mutant of p53 gene are associated with the prognosis of breast infiltrating ductal carcinoma.