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Abstract Objective: The prognostic importance of Tumor-Infiltrating Lymphocytes (TILs) in the tumor microenvironment of various cancers is increasingly recognized. In the present study, we aimed to investigate the prognostic value of CD3+, CD4+, CD8+, and CD45RO + TILs and their relation to histopathological features in larynx squamous cell carcinoma. Methods: Formalin-Fixed and Paraffin-Embedded (FFPE) samples from 63 primary larynx squamous cell carcinoma patients were immunostained for CD3, CD4, CD8, and CD45RO expression. Positive cells in micrographs from Invasive Margin (IM) and Tumor Center (CT) of tissue specimens counted by ImageJ software and their correlation with disease outcome were analyzed. Results: The expression level of TILs subpopulations was associated with clinicopathological markers as well as Overall Survival (OS) and Disease-Free Survival (DFS). In multivariate analysis, high frequency of CD45RO + cells in IM were confirmed as an independent prognostic marker for DFS (p = 0.007, HR = 4.968) and OS (p = 0.007, HR = 4.957). Similar findings were observed in the multivariate analysis of the combined frequency of CD45RO+cells in IM and CT. Conclusion: TILs are associated with patients clinicopathological features. Also, our findings indicate that CD45RO + TILs are a valuable marker for risk prediction in larynx SCC and could predict patients' outcomes.
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BACKGROUND@#Lung cancer is the most common malignancy world-wide. There are a variety of immune infiltrating cells in tumor microenvironment, which is an important component of tumor immunity and has clinical significance for the prognosis of patients. CD45RO is a surface marker of memory T cells. The expression of CD45RO⁺ tumor infiltrating lymphocytes (TILs) is associated with the prognosis of many tumors. The purpose of this study was to evaluate the relationship between the density of CD45RO⁺ TILs in tumor and stromal area and the clinical characteristics of patients with non-small cell lung cancer (NSCLC) and its impact on the prognosis of patients. We aimed to explore the clinical value of CD45RO⁺ TILs and programmed cell death ligand 1 (PD-L1) as prognostic markers.@*METHODS@#Multiple fluorescent immunohistochemical staining was used to stain the tissue microarray chips of 167 patients with NSCLC, marking CD45RO, cytokeratin (CK) and PD-L1. Using artificial intelligence image recognition technology and tumor cell-specific CK staining, divide the tumor and stromal area in the tissue, evaluate the density of CD45RO⁺ TILs in the tumor and stromal area, and the expression level of PD-L1 in tumor cells. The non-parametric test was used to analyze the relationship between CD45RO⁺ TILs and the clinical characteristics of patients, and the Kaplan-Meier method and Cox risk ratio model were used to analyze the relationship between CD45RO⁺ TILs independently or in combination with PD-L1 and tumor prognosis.@*RESULTS@#The density of CD45RO⁺ TILs was significantly associated with patient age, smoking, tumor stage, and pathological type. Single-factor survival analysis showed that NSCLC (P=0.007) stromal region and lung adenocarcinoma (LUAD) (P<0.001) with CD45RO⁺ TILs high density had better OS. Multivariate survival analysis showed that the high density of CD45RO⁺ TILs in the stromal region of NSCLC (HR=0.559, 95%CI: 0.377-0.829, P=0.004) and lung adenocarcinoma (HR=0.352, 95%CI: 0.193-0.641, P=0.001) were independent prognostic factors for overall survival time (OS). Combined with PD-L1 score of tumor cells in tumor tissues and infiltration score of CD45RO⁺ TILs in all tumor tissues, the patients were divided into 4 groups: patients with PD-L1⁺/CD45RO⁺ had the longest disease-free survival (DFS) time, and patients with PD-L1⁺/CD45RO- had the shortest DFS time. Multivariate Cox regression analysis showed that PD-L1⁺/CD45RO- was an independent prognostic factor for DFS and had a higher risk of poor prognosis compared to the other three groups (HR=2.221, 95%CI: 1.258-3.919, P=0.006).@*CONCLUSIONS@#In tumor tissues, the density of CD45RO⁺ TILs, as well as the combination of CD45RO⁺ TILs and PD-L1 in tumor areas, significantly correlated with clinicopathological features and prognosis of NSCLC, which can be used as a new prognosis marker.
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Objective:To investigate the expression of IL-2/IL-15 receptor β subunit (IL-2/IL-15Rβ) on memory CD3 + CD8 + CD45RO + T cells in patients with chronic hepatitis B (CHB) receiving antiviral treatment and its significance. Methods:Sixty-eight patients with chronic active hepatitis B (CAHB) and 47 asymptomatic hepatitis B virus (HBV) carriers attending in the Department of Infectious Diseases, the First Affiliated Hospital of Wannan Medical College from March 2019 to December 2020 were enrolled in the study; and 30 health subjects were also enrolled as healthy control group. Among 60 CAHB patients there were 30 cases with positive HBeAg and 30 cases with negative HBeAg. All CAHB patients received nucleos(t)ide analogue therapy, the HBV-related markers, Alanine aminotransferase (ALT) and the expression of IL-2/IL-15Rβ on CD3 + CD8 + CD45RO + T cells were determined and compared between HBeAg-positive and negative patients, before and after treatment. Normal distribution measurement data among 3 groups were compared with One-way ANOVA; normal distribution measurement data between 2 groups were compared with paired samples t test; non-normal distribution measurement data between the two groups were compared with Mann-Whitney U test; Pearson’s correlation coefficient was performed for correlation analysis. P<0.05 was considered statistically significant. Results:The proportion of CD8 + CD45RO + T cells on PBMC CD3 + T cells in CAHB group [(8.6±3.7)%] was higher than that of asymptomatic HBV carriers group [(5.7±2.5)%] and healthy control group [(5.5±1.5)%] (all P<0.05). The expression percentage of IL-2/IL-15Rβ on PBMC CD3 + CD8 + CD45RO + T cells in CAHB group [(6.8±4.7)%] was higher than that of asymptomatic HBV carriers group [(4.7±2.8)%] and healthy control group [(4.3±2.2)%] (all P<0.05). The MFI of IL-2/IL-15Rβ on PBMC CD3 + CD8 + CD45RO + T cells in CAHB group (243±168) was higher than those of asymptomatic HBV carriers group (160±91) and healthy control group [160±63] (all P<0.05). The expression percentage and MFI of IL-2/IL-15Rβ on PBMC CD3 + CD8 + CD45RO + T cells were positively correlated with the percentage of CD3 + CD8 + CD45RO + T cells in CAHB patients ( r=0.33 and 0.28, all P<0.05). The proliferation percentage of PBMC CD3 + CD8 + CD45RO + T cells in CAHB group[ (43.7±16.0)%] was higher than that of asymptomatic HBV carriers group [(29.1±9.4)%] and healthy control group [(26.8±9.6)%] after stimulation with Anti-CD3+ super-2 (all P<0.05). After the expression of IL-2/IL-15Rβ was blocked, the proliferation percentage of CD3 + CD8 + CD45RO + T cells was decreased [(11.2±6.3)%] compared with the untreated CAHB group ( P<0.05). The percentages of PBMC CD3 + CD8 + CD45RO + T cells secreting IFN-γ, IL-2 and TNF-α in CAHB group were (13.8±5.4)%, (14.0±4.3)% and (12.3±4.6)% respectively, which were higher than those of asymptomatic HBV carriers [(8.4±2.6)%, (9.4±3.2)% and (6.8±3.3)%] and healthy control group [(6.9±2.7)%, (9.9±3.0)% and (7.7±3.8)%] after stimulation with Anti-CD3+ super-2 (all P<0.05). After the expression of IL-2/IL-15Rβ was blocked, the percentages of PBMC CD3 + CD8 + CD45RO + T cells secreting IFN-γ [(2.4±1.6)%], IL-2 [(4.1±1.9)%] and TNF-α [(4.1±1.8)%] were decreased compared with the untreated CAHB group (all P<0.05). HBeAg, ALT, the expression percentage and MFI of IL-2/IL-15Rβ on CD3 + CD8 + CD45RO + T cells were 521.4 (68.9, 1 339.0) COI, 292 (160, 528) U/L, (6.4±3.2)% and (239±136) in 30 HBeAg-positive CAHB patients before treatment, which were higher than those after treatment [3.5(1.5, 17.5)COI、20(14, 31) U/L, (4.1±2.4)% and (134±58)] ( Z=5.337 and 6.403, t=3.229 and 3.892, all P<0.05). HBsAg, ALT, the expression percentage and MFI of IL-2/IL-15Rβ on CD3 + CD8 + CD45RO + T cells were (5 310±2 851) COI, (328±207) U/L, (7.1±5.8)% and (252±110) in 30 HBeAg-negative CAHB patients before treatment, which were higher than those after 48 weeks of treatment [(3 811±2 495) COI, (33±14) U/L, (4.6±2.9)% and (154±73)] ( t=2.167, 5.595, 2.116 and 2.383, all P<0.05). Conclusion:The study suggests that up-regulated expression of IL-2/IL-15Rβ is associated with elevated frequency, proliferation and secretion function of memory CD3 + CD8 + CD45RO + T cells in CAHB patients.
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Background: The most fundamental trait of cancer cells involves their ability to sustain chronic proliferation. Tumors have a complex cellular ecology that establishes the malignant potential of the tumor. In these ecosystems, innate immune cells are highly represented. Many contradictory reports have been published regarding the impact of tumor-infiltrating immune cells on proliferation of the tumors. Aim: This study aims to assess the impact of CD45RO+ve immune cells on proliferation and dedifferentiation of node-negative squamous cell carcinomas of cheek mucosa (SCC-CM). Materials and Methods: Thirty formalin-fixed paraffin-embedded tissue blocks of previously diagnosed node-negative SCC-CM subclassified as Grade I SCC – 10 cases; Grade II SCC – 10 cases; and Grade III SCC – 10 cases (Broders' classification – 1927). Immunohistochemistry performed on each selected tissue section using anti-p53 and anti-CD45RO as primary antibodies. Semi-quantitative analyses performed for all the tissue sections to assess the p53 and CD45RO expression. p53:CD45RO expression ratio calculated. The data were statistically analyzed using GraphPad Prism 5 for Windows. Results: Our results showed statistically significant increase (P = 0.0006) in p53 expression and decrease (P = 0.0044) in CD45RO+ immune cell response with the decrease in differentiation of SCC-CMs using Fisher's exact test and statistically significant increase (P < 0.001) in p53:CD45RO expression ratio with decrease in differentiation using one-way ANOVA. Conclusion: Based on all these findings from the present study, we perceive the following findings. In node-negative SCC-CMs, CD45RO+ immune cells play a possible role in controlling the dedifferentiation of the tumor and in limiting the proliferative potential of the tumor cells which are tumor antagonistic in nature
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Objective@#To investigate the expressions of CD4+CD45RA+ T cells and CD4+CD45RO+ T cells in peripheral blood of patients with acute coronary syndrome (ACS) and their significance.@*Methods@#A case-control study was conducted. Ninety-four patients receiving coronary angiography (CAG) admitted to Tianjin Chest Hospital from March 5th to April 27th in 2018 were enrolled. They were divided into non-coronary heart disease (CHD) group (n = 12), unstable angina pectoris (UAP) group (n = 27), acute non-ST elevation myocardial infarction (NSTEMI) group (n = 27) and acute ST elevation myocardial infarction (STEMI) group (n = 28) according to the patients' symptoms, electrocardiogram, troponin test and angiographic results. General data, blood routine parameters, and biochemical indicators were collected. The ratios of CD4+CD45RA+ T cells and CD4+CD45RO+ T cells were determined by flow cytometry. Multivariate Logistic regression was used to evaluate whether CD4+CD45RA+ T cells and CD4+CD45RO+ T cells were associated with STEMI.@*Results@#Ninety-four patients were included initially. After excluding the patients who died during the intervention, 93 patients were enrolled in the data analysis finally, with 12 patients in the non-CHD group, 27 patients in the UAP group, and the same as the NSTEMI group and the STEMI group. Compared with the non-CHD group, white blood cell count (WBC) was decreased (×109/L: 6.03±1.30 vs. 6.60±1.30, P > 0.05), and lymphocyte ratio was increased (0.273±0.059 vs. 0.269±0.070, P > 0.05) in patients of the UAP group; however, in the NSTEMI group and STEMI group, WBC was increased (×109/L: 8.29±2.28, 9.86±2.76 vs. 6.60±1.30, both P < 0.05), and lymphocyte ratio was decreased (0.236±0.076, 0.173±0.094 vs. 0.269±0.070, P > 0.05 and P < 0.05), especially in the STEMI group [WBC (×109/L): 9.86±2.76 vs. 6.60±1.30, lymphocyte ratio: 0.173±0.094 vs. 0.269±0.070, both P < 0.05]. There was no significant difference in biochemical indicators among all of the groups. Flow cytometry results showed that the ratios of CD4+CD45RO+ T cells in the UAP group and NSTEMI group were higher than those in the non-CHD group (0.323±0.074, 0.319±0.078 vs. 0.314±0.058, both P > 0.05); however, the ratio of CD4+CD45RO+ T cells in the STEMI group showed a decreased tendency (0.270±0.057 vs. 0.314±0.058, P > 0.05), and it was significantly lower than that in the UAP group and the NSTEMI group (0.270±0.057 vs. 0.323±0.074, 0.319±0.078, both P < 0.05). There was no significant difference in the ratio of CD4+CD45RA+ T cells among all of the groups. Multivariate Logistic regression analysis showed that CD4+CD45RA+ T cells ratio was not significantly correlated with the occurrence of STEMI [odds ratio (OR) = 0.976, 95% confidence interval (95%CI) was 0.907-1.050, P = 0.518], but CD4+CD45RO+ T cells ratio was significantly correlated with the occurrence of STEMI (OR = 0.888, 95%CI was 0.821-0.961, P = 0.003).@*Conclusions@#There was no significant difference in the ratio of CD4+CD45RA+ T cells among UAP, NSTEMI and STEMI patients, and CD4+CD45RO+ T cells ratio in the STEMI group was significantly lower than that in the UAP group and NSTEMI group. CD4+CD45RO+ T cells ratio may be risk factor of STEMI.
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Objective To investigate the expressions of CD4+CD45RA+ T cells and CD4+CD45RO+ T cells in peripheral blood of patients with acute coronary syndrome (ACS) and their significance. Methods A case-control study was conducted. Ninety-four patients receiving coronary angiography (CAG) admitted to Tianjin Chest Hospital from March 5th to April 27th in 2018 were enrolled. They were divided into non-coronary heart disease (CHD) group (n = 12), unstable angina pectoris (UAP) group (n = 27), acute non-ST elevation myocardial infarction (NSTEMI) group (n = 27) and acute ST elevation myocardial infarction (STEMI) group (n = 28) according to the patients' symptoms, electrocardiogram, troponin test and angiographic results. General data, blood routine parameters, and biochemical indicators were collected. The ratios of CD4+CD45RA+ T cells and CD4+CD45RO+ T cells were determined by flow cytometry. Multivariate Logistic regression was used to evaluate whether CD4+CD45RA+ T cells and CD4+CD45RO+ T cells were associated with STEMI. Results Ninety-four patients were included initially. After excluding the patients who died during the intervention, 93 patients were enrolled in the data analysis finally, with 12 patients in the non-CHD group, 27 patients in the UAP group, and the same as the NSTEMI group and the STEMI group. Compared with the non-CHD group, white blood cell count (WBC) was decreased (×109/L: 6.03±1.30 vs. 6.60±1.30, P > 0.05), and lymphocyte ratio was increased (0.273±0.059 vs. 0.269±0.070, P > 0.05) in patients of the UAP group; however, in the NSTEMI group and STEMI group, WBC was increased (×109/L: 8.29±2.28, 9.86±2.76 vs. 6.60±1.30, both P < 0.05), and lymphocyte ratio was decreased (0.236±0.076, 0.173±0.094 vs. 0.269±0.070, P > 0.05 and P < 0.05), especially in the STEMI group [WBC (×109/L): 9.86±2.76 vs. 6.60±1.30, lymphocyte ratio: 0.173±0.094 vs. 0.269±0.070, both P < 0.05]. There was no significant difference in biochemical indicators among all of the groups. Flow cytometry results showed that the ratios of CD4+CD45RO+ T cells in the UAP group and NSTEMI group were higher than those in the non-CHD group (0.323±0.074, 0.319±0.078 vs. 0.314±0.058, both P > 0.05); however, the ratio of CD4+CD45RO+ T cells in the STEMI group showed a decreased tendency (0.270±0.057 vs. 0.314±0.058, P > 0.05), and it was significantly lower than that in the UAP group and the NSTEMI group (0.270±0.057 vs. 0.323±0.074, 0.319±0.078, both P < 0.05). There was no significant difference in the ratio of CD4+CD45RA+ T cells among all of the groups. Multivariate Logistic regression analysis showed that CD4+CD45RA+ T cells ratio was not significantly correlated with the occurrence of STEMI [odds ratio (OR) = 0.976, 95% confidence interval (95%CI) was 0.907-1.050, P = 0.518], but CD4+CD45RO+ T cells ratio was significantly correlated with the occurrence of STEMI (OR = 0.888, 95%CI was 0.821-0.961, P = 0.003). Conclusions There was no significant difference in the ratio of CD4+CD45RA+ T cells among UAP, NSTEMI and STEMI patients, and CD4+CD45RO+ T cells ratio in the STEMI group was significantly lower than that in the UAP group and NSTEMI group. CD4+CD45RO+ T cells ratio may be risk factor of STEMI.
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BACKGROUND: Postoperative cholangitis is a common but severe complication after Kasai portoenterostomy for biliary atresia (BA). This study aimed to identify its prognostic factors. METHODS: Two sets of liver paraffin-embedded tissue samples were collected from BA patients who received Kasai portoenterostomy (n = 25 and n = 31, respectively). Patients were divided into non-cholangitis and cholangitis groups. The infiltration of CD4+, CD8+, CD45RO+, CD68+ cells and expression of Beclin1 were quantitatively evaluated in immunohistochemical analysis. RESULTS: Cholangitis group had a significantly lower CD8+ T cell infiltration but a higher CD45RO+ cell infiltration, and a lower Beclin1 level than non-cholangitis group (all P < 0.01). Multivariate logistic regression analysis indicated that infiltration of CD8+ cells (odds ratio [OR], 0.112; 95% confidence interval [CI], 0.022–0.577) and CD45RO+ cells (OR, 3.88; 95% CI, 1.37–11.03), and Beclin1 level (OR, 0.088; 95% CI, 0.018–0.452) were independent influence factors for early postoperative cholangitis. Receiver operating characteristic (ROC) analysis showed that area under ROC curve (AUROC) values for CD8+ cells, CD45RO+ cells and Beclin1 were 0.857, 0.738 and 0.900, respectively. CONCLUSION: Our findings demonstrated the CD8+ cells, CD45RO+ cells and Beclin1 level possessed the prognostic value for early postoperative cholangitis following Kasai operation, which may be helpful to develop new prevention and treatment strategies for postoperative cholangitis.
الموضوعات
Humans , Biliary Atresia , Cholangitis , Liver , Logistic Models , ROC Curve , T-Lymphocytesالملخص
Objective:To explore the role CD4+CD45RO+memory T cells in the pathogenesis of Hashimoto's thyroiditis (HT) by detecting the percentages of CD4+CD45RO+ memory T cells in peripheral blood mononuclear cells in peripheral blood of newly diagnosed HT patients. Methods:53HT patients and 43 matched healthy controls (HC) were included in this study. According to the thyroid functions,HT patients were divided into euthyroid subset(HT-A,n =15) ,subclinical hypothyroidism(HT-B,n=14) and overt hypothyroidism subset (HT-C,n=24). The percentages of CD4+CD45RO+memory T cells in PBMCs,as well as the level of serum IFN-γ and IL-17,and thyroid functions,and the titers of thyroid-specific autoantibodies (TPOAb,TgAb) were respectively detected by flow cytometry,ELISA,and ECLIA. Results:The percentages of CD4+CD45RO+ memory T cells in PBMCs,as well as the level of serum IFN-γ and IL-17,the titers of TPOAb,TgAb were all significantly higher than that in HC(P<0. 01). Bivariate correlation revealed that the percentages of CD4+CD45RO+ memory T cells positively correlated with the level of serum IFN-γ,TPOAb and TgAb(P<0. 01,P=0. 015,P<0. 01) in HT patients. Conclusion:The significant increase of CD4+CD45RO+memory T cells in peripheral blood of patients with HT suggested a role of CD4+CD45RO+ memory T cells in the pathogenesis of this disease.
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To characterize the CD45RA+and CD45RO+T lymphocyte subsets in the peripheral blood of patients with cGVHD induced by allogeneic haematopoietic stem cell transplantation ( allo-HSCT ) and to explore their relations with the disease.Methods:The peripheral blood was collected from 64 patients after allo-HSCT,including 21 non-cGVHD patients,15 light grade cGVHD patients,18 mild grade cGVHD patients and 10 severe grade cGVHD patients,then CD4+CD45RA+,CD4+CD45RO+, CD8+CD45RA+and CD8+CD45RO+T lymphocyte subsets were detected by flow cytometry ( FCM).Results: Compared with the control,the percent of CD4+CD45RA+T lymphocyte in patients with light,mild and severe grade cGVHD decreased markedly (P<0.05),the percent of CD4+CD45RO+T lymphocyte increased markedly (P<0.05).But there were not obviously change in the patient with different grade cGVHD.The percent of CD8+CD45RA+,CD8+CD45RO+T lymphocyte did not change obviously.Conclusion:CD4+CD45RA+and CD4+CD45RO+may play an important role in the pathogenesis of cGVHD.
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Objective:To investigate the infiltration of CD45RO+ T cells and CD68+ cells in the lesions of non-neoplastic epithelial disorder and in vulva cancer.Methods:The infiltration of CD45RO+ T cells and CD68+ cells was detected with S-P immunohistochemistry in the lesions of 20 non-neoplastic epithelial disorders,including vulvar squamous cell hyperplasia(SH) and vulvar lichen sclerosus(LS)) and vulvar cancer,respectively.The vulvar skins from 10 healthy individuals were selected as the control.Results:The infiltration of CD45RO+ T cells and CD68+ cells in healthy vulvar skin was very low and significantly lower than that in SH,LS and vulvar cancer(P0.05).The number of both cells were significantly higher than that in SH,poorly vulvar cancer and early stage of LS(P0.05).The infiltration of CD68+ cells was shown in a positive correlation with CD45RO+ T cells in the different lesion of vulva,the correlation coefficient was 0.742(P
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Objective:To characterize the CD4+CD45RA+,CD4+CD45RO+,CD8+CD45RA+ and CD8+CD45RO+T lymphocyte subsets in the peripheral blood of the patients with chronic hepatitis B and to explore their relations with the disease state.Methods:The peripheral blood was collected from 104 patients with chronic hepatitis B and 30 healthy individuals,then CD4+CD45RA+,CD4+CD45RO+,CD8+CD45RA+ and CD8+CD45RO+T lymphocyte subsets were detected by flow cytometry with three-color fluorescence technology.Results:To compare with the control,the percent of CD8+CD45RA+T lymphocyte in patients with mild and severe grad CHB decreased markedly,the percent of CD8+CD45RO+T lymphocyte increased markedly,CD4+,CD8+,CD4+CD45RA+ and CD4+CD45RO+T lymphocyte did not change obviously. Compared with the mild grade CHB,the percent of CD8+CD45RA+T lymphocyte in patients with severe grade CHB decreased obviously(P
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Objective:To study the changes of lymphocytes subpopulation and apoptosis process of lymphocytes in the elderly and to investigate the modulatory effect of BP from Chinese herb on apoptosis.Methods:Lymphocytes phenotype were determinated using indirect immunofluorescence technique.The proliferative responses were measured with MTT method.Apoptosis of lymphocytes was evaluated by flow cytometry and automatic image analysis.Results:The proliferative responses of lymphocytes in the elderly were lower than that of young adults.Decreased CD45RA positive cells and increased CD 45 RO positive cells were found in lymphocytes population of aged people compared to that of young adults. The CD 45 PO positive cells were prone to apoptosis.There is an imhibitory effect of BP on apoptosis of lymphocytes in the elderly.Conclusion:It was implicated that the susceptibility of lymphocyte in the elderly to apoptosis depends on activation,so called activation induced cell death.Present results suggested that apoptosis of lymphocytes of aged people play an important role in the pathogenesis of immunosenescence.The possibility appeared for development of modulatory drugs on apoptosis from Chinese herbs.