The Predictive Value of Changes in the Absolute Counts of Peripheral Lymphocyte Subsets for Progression and Prognosis in Breast Cancer Patients.

Background: As the number and proportion of lymphocyte subsets are an important indicator of the immune function, an in depth understanding of the immune function of patients with malignant tumor has important clinical values for the treatment, prognosis, and evaluation of the disease. This retrospective study was to evaluate the clinical value of the absolute counts of lymphocyte subsets as potential blood biomarkers for progression and prognosis in breast cancer patients. Methods: A total of 237 BC patients and 55 age-matched female normal healthy donors were included in this study. Flow cytometry was used to determine the absolute counts and the percentages of CD3+, CD4+, CD8+, B, and NK cells. The receiver operating characteristic curve (ROC) was used to evaluate the accuracy of absolute count of lymphocyte subsets in the curative efficacy assessment. The clinicopathological parameters influencing the disease progression were determined by Cox proportional hazards regression. Progression-free survival (PFS) was estimated using the Kaplan-Meier method with the log-rank test. Results: Compared with the healthy donors, the absolute counts of lymphocyte subsets in patients decreased significantly. ROC analysis showed that the area under the curve of the CD4+ absolute count was 90% (95% confidence interval 0.859-0.940), and the sensitivity and specificity were 80.9% and 85.3%, respectively. The analysis of Cox regression showed that the cutoff value of the CD4+ absolute count ≥451 cells/µL might be a favorable prognostic factor. Multivariate analysis of prognostic factors of PFS showed that the CD4+ and CD8+ absolute count were independent factors for predicting PFS. Conclusions: The remarkably impaired absolute counts of the CD3+, CD4+, CD8+, B, and NK cells in patients with breast cancer can be used as potential susceptible biomarkers to evaluate the patient's immune status. The higher level of CD4+ and CD8+ absolute counts probably contributed to the longer PFS and favorable outcome of BC patients.

Clinical predictive value of naïve and memory T cells in advanced NSCLC.

Currently, there is no sensitive prognostic biomarker to screen out benefit patients from the non-benefit population in advanced non-small cell lung cancer patients (aNSCLCs). The 435 aNSCLCs and 278 normal controls (NCs) were recruited. The percentages and absolute counts (AC) of circulating naïve and memory T lymphocytes of CD4+ and CD8+ T cells (Tn/Tm) were measured by flow cytometry. The percentage of CD4+ naïve T (Tn), CD8+ Tn, CD8+ T memory stem cell (Tscm), and CD8+ terminal effector T cell decreased obviously. Still, all AC of Tn/Tm of aNSCLCs was significantly lower compared to NCs. Higher AC and percentage of CD4+ Tn, CD8+ Tn, and CD4+ Tscm showed markedly longer median PFS in aNSCLCs. Statistics demonstrated the AC of CD4+ Tn (≥ 3.7 cells/µL) was an independent protective factor for PFS. The analysis of the prognosis of immunotherapy showed the higher AC and percentage of CD4+ Tn and CD4+ Tscm and higher AC of CD8+ Tscm had significantly longer median PFS and the AC of CD4+ Tn (≥ 5.5 cells/µL) was an independent protective factor for PFS. Moreover, higher AC and percentages of Tn/Tm suggested higher disease control rate and lower progressive disease rate. The AC of Tn/Tm showed more regular patterns of impairment and was more relative with the disease progression than percentages in aNSCLCs. AC had a better predictive value than percentages in Tn/Tm for PFS. Notably, the AC of CD4+ Tn was a potential prognostic biomarker for the PFS and efficacy of immunotherapy.

Reference range of naïve T and T memory lymphocyte subsets in peripheral blood of healthy adult.

Naïve T and T memory cell subsets are closely related to immune response and can provide important information for the diagnosis and treatment of immunological and hematological disorders. Lymphocyte compartment undergoes dramatic changes during adulthood; age-related reference values derived from healthy individuals are crucial. However, extensively detailed reference values of peripheral blood lymphocytes in the whole spectrum of adulthood detected by multi-color flow cytometry on a single platform are rare. Three hundred and nine healthy adult volunteers were recruited from Tianjin in China. The absolute counts and percentages of CD3+CD4+ T cells, CD3+CD8+ T cells, naïve T cells (Tn), T memory stem cells (Tscm), central memory T cells (Tcm), effector memory T cells (Tem), and terminal effector T cells (Tte) were detected by flow cytometry with single platform technologies. Reference range of absolute counts and percentage of T lymphocyte subsets were formulated by different age and gender. The results showed that Tn and Tscm cells, which had stem cell properties, decreased with aging; while, Tcm and Tem increased with aging, which increased from 18 to 64 years old but presented no significant change over the 65 years old. Gender had an influence on the fluctuation of lymphocyte subsets, the absolute count of CD3+CD8+, CD8+Tcm, CD8+Tem in males were higher than those in females. The reference values of percentages and absolute numbers of naïve T and T memory cell subsets can help doctors to understand the immune state of patients and evaluate conditions of prognosis then adjust the treatment for patients. (Chinese Clinic Trial Registry number: ChiCTR-IOR-17014139.).

The clinical value of the changes of peripheral lymphocyte subsets absolute counts in patients with non-small cell lung cancer.

INTRODUCTION: Immune function strongly influences the outcome of patients with non-small cell lung cancer (NSCLC). It's vital to understand the immune state of patients through detecting the percentage and number of lymphocyte subsets accurately, and helpful to evaluate conditions of prognosis and adjust treatment for patients. METHODS: We conducted a retrospective cohort study in First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China. The absolute counts and percentages of CD3+, CD3 + CD4+, CD3 + CD8+, B and NK cells were determined by single platform technologies. 172 patients received treatment including surgery or chemotherapy after surgery. The factors affecting disease progression were analyzed by Binary Logistic regression. Progression free survival (PFS) calculating survivals were with the method of Kaplan-Meier. The log-rank test and cox's proportional hazard regression (enter method) were used for univariable and multivariable analyses respectively. RESULTS: Relative to normal controls, patients with NSCLC at different stages showed decreased absolute lymphocyte count obviously, rather than lymphocyte percentages. Different treatments had unlike influence on the homeostasis of lymphocytes and the effects last for a long time. Logistic regression showed CD3 + CD4+ and CD3 + CD8+ could contribute to favorable prognosis. Multivariate analysis of prognostic factors of PFS showed CD3 + CD4+ cell was independent factor for predicting PFS. CONCLUSIONS: The absolute count of CD3+, CD3 + CD4+, CD3 + CD8+, B and NK cells were better indication of the patient's immune state than percentages of each lymphocyte subsets. Immune function was impaired in patients with non-small cell lung. The high level of baseline absolute CD3 + CD4+ cells count contributed to longer progression free survival. Chinese Clinic Trial Registry number: ChiCTR-IOR-17014139; Registry date: 2017/12/25.

Discovery and characteristics of B cell-like T cells: A potential novel tumor immune marker?

BACKGROUND: CD3 and CD19 are the characteristic surface markers of mature T lymphocytes and B lymphocytes of human respectively. A special subset of immune cells that characteristically expressed the surface markers CD19+ of B lymphocytes and CD3+ of T lymphocytes simultaneously (CD19+CD3+ cells, hereinafter referred to as B-T cells) was found in the peripheral blood of human, yet it has not been reported in cancer research before. Our aims were to characterize the expression and possible value of B-T cells in cancer patients. METHODS: Flow cytometry was applied to analyse the CD19+CD3+ cells, and laser scanning confocal microscope was utilized to prove co-expressing CD19+ of B lymphocytes and CD3+ of T lymphocytes simultaneously on the surface of the cells. Then a total of 523 patients with malignant tumor were enrolled in this study, and 177 healthy donors were recruited as the control group. The levels of CD19+CD3+ cells in peripheral blood were measured by flow cytometry, and the differences between the two groups were compared. RESULTS: The healthy donors and cancer patients all had B-T cells in their peripheral blood, but the percentage of B-T cells was 0.16 % ± 0.11 % and 0.58 % ± 0.38 % respectively, showing statistically significant (P < 0.0001). There was no significant correlation between the percentage of B-T cells and lymphocyte subsets (P > 0.05). The percentages of B-T cells in different tumor species were different. The proportion of B-T cells was high in esophageal cancer, non-Hodgkin's lymphoma and lung cancer, but it was low in pancreatic cancer, ovarian cancer and kidney cancer. Meanwhile, there was significant difference between esophageal cancer and kidney cancer (P < 0.001). The distribution of B-T cells in pancreatic cancer and kidney cancer was more concentrated, yet more dispersed in other cancers. Although there was a trend of increase in clinical stage Ⅲ+Ⅳ and a trend of decrease in age above 60 years for breast cancer, gastric cancer and liver cancer, there was no significant difference in the percentage of B-T cells in age, gender, different clinical stages, tumor metastasis, lymph node metastasis, and splenomegaly (P > 0.05). CONCLUSION: The percentage of B-T cells in cancer patients was significantly higher than that of healthy donors. B-T cells maybe play a very complicated role in tumor, whether it could be a potential tumor immune marker or not and what are the specific phenotypes and functions of it to need be further verified.

The association between runt-related transcription factor 3 gene promoter methylation and gastric cancer: A meta-analysis.

OBJECTIVE: To systematically evaluate the relationship of the methylation of the human-runt-related transcription factor 3 (RUNX3) promoter region and gastric cancer risk through meta-analysis. MATERIALS AND METHODS: The studies published in PubMed, EMBASE, Ovid, and CNKI were retrieved. The association between RUNX3 gene promoter methylation and gastric cancer was analyzed using Stata 11.0 (http://www.stata.com; Stata Corporation, College Station, TX, USA) and Review Man 5.0 software (http://ims.cochrane.org/revman/download). RESULTS: Seventeen studies are included in the analysis. Meta-analysis reveals that the odds ratio of the methylation of the RUNX3 promoter region in gastric was 7.32 (95% confidence interval: 5.12-10.47), which was significant higher than the normal gastric tissues (P < 0.05). CONCLUSIONS: The RUNX3 gene promoter methylation rate was much higher in tumor tissue than that in normal gastric tissue in patient with gastric cancer, which indicates a close association between gastric cancer and RUNX3 gene promoter methylation.

Acupuncture for treatment of climacteric syndrome--a report of 35 cases.

OBJECTIVE: To evaluate the effects of acupuncture for treatment of climacteric syndrome. METHODS: The 65 cases in this series were randomly assigned to the acupuncture group (N=35) and the control group (N=30), with the former treated by acupuncture and the latter by medication respectively. The therapeutic effects were evaluated by means of the clinical outcome, improvement in the symptom scores and the results of radioimmunoassays. RESULTS: In the acupuncture group, 12 cases were cured, 16 cases markedly effective, and 6 cases improved, the total effective rate being as high as 97.14%. The decrease in the symptom scores, and especially the elevation of the decreased E2 level and the decrease of the increased FSH and LH levels, demonstrated that acupuncture therapy was superior to medication. CONCLUSION: Acupuncture for regulating the mental activities and reinforcing the kidney is an effective therapy for climacteric syndrome.