1.Clinicopathological characteristics of the CD8+T lymphocytes infiltration and its mechanism in distinct molecular subtype of medulloblastoma
Xiaodong CHAI ; Ziwen SUN ; Haishuang LI ; Liangyi ZHU ; Xiaodan LIU ; Yantao LIU ; Fei PEI ; Qing CHANG
Journal of Peking University(Health Sciences) 2024;56(3):512-518
Objective:To investigate the characteristics of the CD8+T cells infiltration from the 4 sub-types in medulloblastoma(MB),to analyze the relationship between CD8+T cells infiltration and prog-nosis,to study the function of C-X-C motif chemokine ligand 11(CXCL11)and its receptor in CD8+T cells infiltration into tumors and to explore the potential mechanism,and to provide the necessary clinico-pathological basis for exploring the immunotherapy of MB.Methods:In the study,48 clinical MB sam-ples(12 cases in each of 4 subtypes)were selected from the multiple medical center from 2012 to 2019.The transcriptomics analysis for the tumor of 48 clinical samples was conducted on the NanoString Pan-Cancer 10360?Panel(NanoString Technologies).Immunohistochemistry(IHC)staining of formalin-fixed,paraffin-embedded sections from MB was carried out using CD8 primary antibody to analyze diffe-rential quantities of CD8+T cells in the MB four subtypes.Through bioinformatics analysis,the relation-ship between CD8+T cells infiltration and prognosis of the patients and the expression differences of various chemokines in the different subtypes of MB were investigated.The expression of CXCR3 receptor on the surface of CD8+T cells in MB was verified by double immunofluorescence staining,and the under-lying molecular mechanism of CD8+T cells infiltration into the tumor was explored.Results:The charac-teristic index of CD8+T cells in the WNT subtype of MB was relatively high,suggesting that the number of CD8+T cells in the WNT subtype was significantly higher than that in the other three subtypes,which was confirmed by CD8 immunohistochemical staining and Gene Expression Omnibus(GEO)database analysis by using R2 online data analysis platform.And the increase of CD8+T cells infiltration was posi-tively correlated with the patient survival.The expression level of CXCL11 in the WNT subtype MB was significantly higher than that of the other three subtypes.Immunofluorescence staining showed the presence of CXCL11 receptor,CXCR3,on the surface of CD8+T cells,suggesting that the CD8+T cells might be attracted to the MB microenvironment by CXCL11 through CXCR3.Conclusion:The CD8+T cells infiltrate more in the WNT subtype MB than other subtypes.The mechanism may be related to the activation of CXCL11-CXCR3 chemokine system,and the patients with more infiltration of CD8+T cells in tumor have better prognosis.This finding may provide the necessary clinicopathological basis for the regulatory mechanism of CD8+T cells infiltration in MB,and give a new potential therapeutic target for the future immunotherapy of MB.
2.Expression and prognostic value of triggering receptor expressed on myeloid cells-1 in patients with cirrhotic ascites and intra-abdominal infection
Feng WEI ; Xinyan YUE ; Xiling LIU ; Huimin YAN ; Lin LIN ; Tao HUANG ; Yantao PEI ; Shixiang SHAO ; Erhei DAI ; Wenfang YUAN
Journal of Clinical Hepatology 2025;41(5):914-920
ObjectiveTo analyze the expression level of triggering receptor expressed on myeloid cells-1 (TREM-1) in serum and ascites of patients with cirrhotic ascites, and to investigate its correlation with clinical features and inflammatory markers and its role in the diagnosis of infection and prognostic evaluation. MethodsA total of 110 patients with cirrhotic ascites who were hospitalized in The Fifth Hospital of Shijiazhuang from January 2019 to December 2020 were enrolled, and according to the presence or absence of intra-abdominal infection, they were divided into infection group with 72 patients and non-infection group with 38 patients. The patients with infection were further divided into improvement group with 38 patients and non-improvement group with 34 patients. Clinical data and laboratory markers were collected from all patients. Serum and ascites samples were collected, and ELISA was used to measure the level of TREM-1. The independent-samples t test was used for comparison of normally distributed continuous data between two groups; the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups; the chi-square test was used for comparison of categorical data between two groups. A Spearman correlation analysis was used to investigate the correlation between indicators. A multivariate Logistic regression analysis was used to identify the influencing factors for the prognosis of patients with cirrhotic ascites and infection. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic and prognostic efficacy of each indicator, and the Delong test was used for comparison of the area under the ROC curve (AUC). ResultsThe level of TREM-1 in ascites was significantly positively correlated with that in serum (r=0.50, P<0.001). Compared with the improvement group, the non-improvement group had a significantly higher level of TREM-1 in ascites (Z=-2.391, P=0.017) and serum (Z=-2.544, P=0.011), and compared with the non-infection group, the infection group had a significantly higher level of TREM-1 in ascites (Z=-3.420, P<0.001), while there was no significant difference in the level of TREM-1 in serum between the two groups (P>0.05). The level of TREM-1 in serum and ascites were significantly positively correlated with C-reactive protein (CRP), procalcitonin (PCT), white blood cell count, and neutrophil-lymphocyte ratio (r=0.288, 0.344, 0.530, 0.510, 0.534, 0.454, 0.330, and 0.404, all P<0.05). The ROC curve analysis showed that when PCT, CRP, and serum or ascitic TREM-1 were used in combination for the diagnosis of cirrhotic ascites with infection, the AUCs were 0.715 and 0.740, respectively. The multivariate Logistic regression analysis showed that CRP (odds ratio [OR]=1.019, 95% confidence interval [CI]: 1.001 — 1.038, P=0.043) and serum TREM-1 (OR=1.002, 95%CI: 1.000 — 1.003, P=0.016) were independent risk factors for the prognosis of patients with cirrhotic ascites and infection, and the combination of these two indicators had an AUC of 0.728 in predicting poor prognosis. ConclusionThe level of TREM-1 is closely associated with the severity of infection and prognosis in patients with cirrhotic ascites, and combined measurement of TREM-1 and CRP/PCT can improve the diagnostic accuracy of infection and provide support for prognostic evaluation.