RESUMO
CD8+ tumor-infiltrating lymphocytes have been regarded as potential biomarkers for cancer prognosis, while the prognostic effect of CD8+ tumor-infiltrating T cells remains controversial in breast cancer. In the present study, a meta-analysis was performed to evaluate the prognostic value of CD8+ T cells in breast cancer and the associations between CD8+ T cells and the pathological characteristics. The PubMed, Embase and the Cochrane Library were systematically searched entries added from the establishment of the database to November 2021 and prospective or retrospective studies of patients with breast cancer were included. The Newcastle-Ottawa Scale was used to assess the quality of evidence for each study. STATA 15.1 was used for the data analysis. A total of 14 studies comprising 22,222 patients were included in the final analysis and the pooled results suggested that a high CD8+ T-cell infiltration level was significantly related to better overall survival [hazard ratio (HR)=0.70, 95% confidence interval (CI): 0.60-0.82, P<0.001] and disease-free survival (HR=0.63, 95% CI: 0.49-0.81, P<0.001) for patients with breast cancer. In addition, a high CD8+ T-cell infiltration level was significantly associated with decreased expression of estrogen receptor [odds ratio (OR)=1.92, 95% CI: 1.30-2.85, P=0.001] and progesterone receptor (OR=1.66, 95% CI: 1.14-2.42, P=0.008), and increased human epidermal growth factor receptor 2 expression (OR=0.79, 95% CI: 0.66-0.94, P=0.010) in patients with breast cancer, while there was no significant association between CD8+ T-cell infiltration and age, tumor size or lymph node status of patients with breast cancer (P>0.05). In conclusion, CD8+ T-cell infiltration is of prognostic value in patients with breast cancer. High levels of CD8+ T-cell infiltration were related to improved prognosis, including OS and DFS, in patients with breast cancer.
RESUMO
BACKGROUND: T cells express interleukin-2 inducible T-cell kinase (ITK), which is an essential modulator of T-cell signaling and function. However, the role of ITK in solid organ transplantation has not been investigated to date. Here, we studied the function of ITK in a murine cardiac transplantation model. METHOD: Murine heart transplantation was performed using BALB/C mice as donors and C57BL/6 mice as recipients. Subsequent intraperitoneal injections of an ITK-specific inhibitor (BMS-509744) were performed to assess the effects of the kinase following cardiac transplantation. Additionally, naive T cells were isolated to investigate the inhibitor's potential effects in the alloimmune responses. RESULTS: ITK inhibition was found to promote long-term cardiac allograft survival compared with the control group of 36.0 ± 3.8 days vs. 7.0 ± 0.7 days, respectively (P < 0.01). While the Th1/Th17 percentages showed a decrease in prevalence (P < 0.001), the CD4+CD25+Foxp3+ percentages were not markedly affected. In vitro treatment of CD4+ T cells with the ITK inhibitor downregulated the proliferation, possibly by regulating the phosphorylation of PLCγ. CONCLUSION: ITK inhibition resulted in lower Th1/Th17 responses after cardiac transplantation and markedly prolonged the mean survival time of the cardiac allografts. Thus, ITK inhibition might be a promising therapeutic target to alleviate alloimmune responses in the cardiac transplantation.
RESUMO
PURPOSE: To evaluate the risk factors of tricuspid regurgitation (TR) after left-sided valve replacement (LSVR) and plan the initial surgical treatment of TR. METHODS: Two hundred and forty-eight patients, including 217 patients in the LSVR group and 31 patients in the LSVR+DeVega group, were followed up. A retrospective analysis was performed on 14 characteristics in the LSVR group. Variables were used to evaluate predictors of TR progression after single LSVR by either a univariate or multivariate analysis. DeVega's tricuspid annuloplasty was evaluated on progress of TR by univariate analysis. RESULTS: The mean follow-up was 5.2 +/- 2.9 (range, 3-16) years after surgery. In a univariate analysis, atrial fibrillation, huge left atrium, long time from onset to surgery, tricuspid rheumatic changes, preoperative +2 or +3 TR, the degradation of left ventricular ejection fraction, augmented right atrium, and single mitral valvular disease were significant risk factors for TR development. A multivariate analysis indicated that the four items mentioned above were statistically significant predictors of TR after surgery. The progress of TR in the LSVR+DeVega group was significantly less than in the LSVR group. CONCLUSIONS: An aggressive repair of accompanying TR should be performed at the time of initial surgery in patients with a huge left atrium, atrial fibrillation, long time from onset to surgery, or tricuspid rheumatic changes. DeVega's tricuspid annuloplasty therefore helps prevent a progression of TR.
