scholarly journals BCR–ABL-specific CD4+ T-helper cells promote the priming of antigen-specific cytotoxic T cells via dendritic cells

2016 ◽  
Vol 15 (1) ◽  
pp. 15-26 ◽  
Author(s):  
Norihiro Ueda ◽  
Rong Zhang ◽  
Minako Tatsumi ◽  
Tian-Yi Liu ◽  
Shuichi Kitayama ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Helper Cells ◽  
Cytotoxic T Cells ◽  
T Helper ◽  
Helper Cells

scholarly journals Interplay between glucocorticoids and tumor-infiltrating lymphocytes on the prognosis of adrenocortical carcinoma

2020 ◽  
Vol 8 (1) ◽  
pp. e000469 ◽  
Author(s):  
Laura-Sophie Landwehr ◽  
Barbara Altieri ◽  
Jochen Schreiner ◽  
Iuliu Sbiera ◽  
Isabel Weigand ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cells ◽  
Adrenocortical Carcinoma ◽  
T Helper Cells ◽  
Checkpoint Inhibitors ◽  
Cytotoxic T Cells ◽  
Adrenal Tumors ◽  
T Helper ◽  
Primary Tumors ◽  
Helper Cells

BackgroundAdrenocortical carcinoma (ACC) is a rare endocrine malignancy. Tumor-related glucocorticoid excess is present in ~60% of patients and associated with particularly poor prognosis. Results of first clinical trials using immune checkpoint inhibitors were heterogeneous. Here we characterize tumor-infiltrating T lymphocytes (TILs) in ACC in association with glucocorticoids as potential explanation for resistance to immunotherapy.MethodsWe performed immunofluorescence analysis to visualize tumor-infiltrating T cells (CD3+), T helper cells (CD3+CD4+), cytotoxic T cells (CD3+CD8+) and regulatory T cells (Tregs; CD3+CD4+FoxP3+) in 146 ACC tissue specimens (107 primary tumors, 16 local recurrences, 23 metastases). Quantitative data of immune cell infiltration were correlated with clinical data (including glucocorticoid excess).Results86.3% of ACC specimens showed tumor infiltrating T cells (7.7 cells/high power field (HPF)), including T helper (74.0%, 6.7 cells/HPF), cytotoxic T cells (84.3%, 5.7 cells/HPF) and Tregs (49.3%, 0.8 cells/HPF). The number of TILs was associated with better overall survival (HR for death: 0.47, 95% CI 0.25 to 0.87), which was true for CD4+− and CD8+subpopulations as well. In localized, non-metastatic ACC, the favorable impact of TILs on overall and recurrence-free survival was manifested even independently of ENSAT (European Network for the Study of Adrenal Tumors) stage, resection status and Ki67 index. T helper cells were negatively correlated with glucocorticoid excess (Phi=−0.290, p=0.009). Patients with glucocorticoid excess and low TILs had a particularly poor overall survival (27 vs. 121 months in patients with TILs without glucocorticoid excess).ConclusionGlucocorticoid excess is associated with T cell depletion and unfavorable prognosis. To reactivate the immune system in ACC by checkpoint inhibitors, an inhibition of adrenal steroidogenesis might be pivotal and should be tested in prospective studies.

Preferential accumulation of T helper cells but not cytotoxic T cells characterizes benign subclinical rejection of human liver allografts

2016 ◽  
Vol 22 (7) ◽  
pp. 943-955 ◽  
Author(s):  
Anna K. Baumann ◽  
Jerome Schlue ◽  
Fatih Noyan ◽  
Matthias Hardtke-Wolenski ◽  
Frank Lehner ◽  
...  
Keyword(s):  
T Cells ◽  
T Helper Cells ◽  
Human Liver ◽  
Cytotoxic T Cells ◽  
T Helper ◽  
Helper Cells ◽  
Preferential Accumulation ◽  
Subclinical Rejection ◽  
Human Liver Allografts

scholarly journals P03.01 Prevalence of CD112R+immune cells in normal lymphatic tissues, inflammation and the cancer microenvironment

2020 ◽  
Vol 8 (Suppl 2) ◽  
pp. A22.1-A22
Author(s):  
NC Blessin ◽  
T Mandelkow ◽  
E Bady ◽  
C Hube-Magg ◽  
R Simon ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Immune Cells ◽  
T Helper Cells ◽  
Checkpoint Inhibitors ◽  
Cytotoxic T Cells ◽  
Small Subset ◽  
Cancer Microenvironment ◽  
T Helper ◽  
Helper Cells

BackgroundCD112R is an inhibitory immune checkpoint receptor and a putative target for novel immune therapies, but little is known about its molecular epidemiology in healthy and diseased tissues.Materials and MethodsTo study the prevalence and expression level of CD112R+ immune cells, we analyzed more than 200 samples of normal lymphatic, inflamed and cancerous tissues in a microenvironment tissue microarray format (4 mm tissue spot diameter) and large sections using fluorescent multiplex immunohistochemistry.ResultsCD112R expression was detected at variable intensity levels in 47% of CD8+ cytotoxic lymphocytes, 49% of CD4+ T helper cells, 30% of FOXP3+ regulatory T helper cells and in 25% of CD56+ natural killer cells, but no expression was seen in CD11c+ dendritic cells and CD68+ macrophages. All analyzed compartments across normal and diseased tissues showed a small subset (CD8: 9±18%, CD4: 5±15%, FOXP3: 2±5%) of immune cells with supramaximal CD112R expression. The highest fraction of cells with supramaximal CD112R expression was found in the subset of CD8+ cytotoxic T cells in the Peyer’s patches of ileum (62%), the intergranuloma area of lymph node sarcoidosis (27%) and in ovarian cancer (37%). In cancerous tissues, the density and the fraction cytotoxic T cells with supramaximal CD112R expression was highly variable and ranged from 5% in bladder cancer to 3% in lung cancer and 36% in ovarian cancer. A high variability of the number of cells with supramaximal CD112R expression was also seen within every tumor entity.ConclusionsIn summary, our analysis shows that CD112R expression is abundant in various subsets of immune cells but identifies a small fraction of cells with exceedingly high CD112R levels. The widespread occurrence of CD112R+ cytotoxic T cells in the cancer microenvironment may suggest considerable opportunities for checkpoint inhibitors targeting CD112R.Disclosure InformationN.C. Blessin: None. T. Mandelkow: None. E. Bady: None. C. Hube-Magg: None. R. Simon: None. G. Sauter: None. C. Fraune: None. M. Lennartz: None. K. Möller: None. D. Höflmayer: None. S.A. Weidemann: None.

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