scholarly journals Analysis of Regulatory T-cells-specific mRNAs for Improving Prognosis, Immunotherapy Response and Therapeutic Resistance of Patients With Prostate Cancer

2021 ◽  
Author(s):  
Mingyi Ju ◽  
Jingyi Fan ◽  
Yuanjiang Zou ◽  
Mingjie Yu ◽  
Longyang Jiang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Cancer Patients ◽  
Tumor Immunity ◽  
Immune Cell ◽  
Cell Types ◽  
Therapeutic Resistance ◽  
Prognostic Signature ◽  
Specific Mrnas

Abstract Background: Prostate cancer recognized as a “cold” tumor has an immunosuppressive microenvironment in which regulatory T-cells (Tregs) usually represent a major role. Therefore, identifying a prognostic signature of Tregs has promising benefits of improving survival of prostate cancer patients. However, the prognostic signature based on Tregs-specific mRNAs for prostate cancer is lacking. Methods: We systematicly analyzed transcriptional profiles of Tregs and 19 other immune cell types using 42 purified immune cell datasets from GEO to identify Tregs-specific mRNAs, and develop and validate a prognostic signature of Tregs (named “TILTregSig”) for monitoring prognosis of prostate cancer using TCGA and ICGC datasets. We also applied the signature to five immunotherapy response datasets and GSCALite to analyze the potential of the TILTregSig for predicting CIT response and cancer therapeutic resistance.Results: We develop the TILTregSig comprising five mRNAs (SOCS2, EGR1, RRM2, TPP1 and C11orf54) for prostate cancer patients. We find that the TILTregSig is a stronger predictor for tumor immunity compared with tumor mutation burden (TMB) and glycolytic activity which have been reported as immune predictors. Further analyses indicate that the TILTregSig may influence tumor immunity mainly by mediating tumor-infiltrating Tregs. Moreover, the TILTregSig also shows promising potential for predicting cancer immunotherapy (CIT) response and therapeutic resistance in multiple cancers.Conclusions: Our study has highlighted the value of the TILTregSig as a prognostic biomarker of prostate cancer from a tumor-infiltrating Tregs perspective, and strengthened its potential application as predictor of CIT response and cancer therapeutic resistance, which warrants further.

Immunosuppressive milieu of high-risk localized prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 344-344
Author(s):  
Victor Ricardo Adorno Febles ◽  
Dennis Adeegbe ◽  
Aarif Ahsan ◽  
Jiansheng Wu ◽  
Alireza Khodadad-Jamayran ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Immune Cell ◽  
Histological Grade ◽  
Statistical Significance ◽  
Cell Types ◽  
Localized Prostate Cancer

344 Background: The immune factors that modulate the aggressiveness of localized treatment-naïve prostate cancer remain poorly understood. Methods: Fresh tumor and peripheral blood were collected at the time of radical prostatectomy in patients with localized prostate cancer. We evaluated the immune cell composition of 22 patient samples employing multi-parametric flow cytometry. Samples were grouped by histological grade into intermediate (INTPCA) and high-grade (HIGHPCA) prostate cancers based on standard NCCN criteria and immune cell abundances were quantified by mean +/- SEM. Statistical significance was assessed using the Mann-Whitney test. Results: INTPCA and HIGHPCA tumors harbored a similar increase in CD8+ T cells ( p < 0.0005 and p < 0.05, respectively) and CD11b+CD68-CD16+ myeloid-derived cells (p < 0.05) relative to the peripheral blood. Other cell types were similarly decreased in both INTPCA and HIGHPCA, including CD11b+CD68+CD14+ ( p < 0.005 and p < 0.05, respectively). By contrast, regulatory T cells were the only cell type in our analysis to be uniquely enriched in HIGHPCA rather than INTPCA ( p < 0.05). The most unique feature found in phenotypic profiling of the immune repertoire of HIGHPCA relative to INTPCA was an increase in the immune inhibitory receptor ligand, PD-L1, in the tumor associated macrophages (CD11b+CD68+CD14+) compared to the periphery (p < 0.05). Conclusions: Collectively, our findings reveal that HIGHPCA harbors a distinct immunological landscape. Although effector CD8+ T cells are preferentially expressed in the tumor, these are met with an increased proportion of regulatory T cells as well as PD-L1 expressing macrophages that contribute to the inert tumor microenvironment. These are key features of aggressive prostate cancer that may serve as potential biomarkers and therapeutic targets.

scholarly journals Single-Cell Sequencing of Mouse Heart Immune Infiltrate in Pressure Overload–Driven Heart Failure Reveals Extent of Immune Activation

Circulation ◽  
2019 ◽  
Vol 140 (25) ◽  
pp. 2089-2107 ◽  
Author(s):  
Elisa Martini ◽  
Paolo Kunderfranco ◽  
Clelia Peano ◽  
Pierluigi Carullo ◽  
Marco Cremonesi ◽  
...  
Keyword(s):  
Heart Failure ◽  
T Cells ◽  
Mast Cells ◽  
Natural Killer Cells ◽  
Regulatory T Cells ◽  
Natural Killer ◽  
Immune Activation ◽  
Immune Cell ◽  
Pressure Overload ◽  
Cell Types

Background: Inflammation is a key component of cardiac disease, with macrophages and T lymphocytes mediating essential roles in the progression to heart failure. Nonetheless, little insight exists on other immune subsets involved in the cardiotoxic response. Methods: Here, we used single-cell RNA sequencing to map the cardiac immune composition in the standard murine nonischemic, pressure-overload heart failure model. By focusing our analysis on CD45 + cells, we obtained a higher resolution identification of the immune cell subsets in the heart, at early and late stages of disease and in controls. We then integrated our findings using multiparameter flow cytometry, immunohistochemistry, and tissue clarification immunofluorescence in mouse and human. Results: We found that most major immune cell subpopulations, including macrophages, B cells, T cells and regulatory T cells, dendritic cells, Natural Killer cells, neutrophils, and mast cells are present in both healthy and diseased hearts. Most cell subsets are found within the myocardium, whereas mast cells are found also in the epicardium. Upon induction of pressure overload, immune activation occurs across the entire range of immune cell types. Activation led to upregulation of key subset-specific molecules, such as oncostatin M in proinflammatory macrophages and PD-1 in regulatory T cells, that may help explain clinical findings such as the refractivity of patients with heart failure to anti–tumor necrosis factor therapy and cardiac toxicity during anti–PD-1 cancer immunotherapy, respectively. Conclusions: Despite the absence of infectious agents or an autoimmune trigger, induction of disease leads to immune activation that involves far more cell types than previously thought, including neutrophils, B cells, Natural Killer cells, and mast cells. This opens up the field of cardioimmunology to further investigation by using toolkits that have already been developed to study the aforementioned immune subsets. The subset-specific molecules that mediate their activation may thus become useful targets for the diagnostics or therapy of heart failure.

Depletion of regulatory T cells by anti-ICOS antibody enhances anti-tumor immunity of tumor cell vaccine in prostate cancer

Vaccine ◽  
2017 ◽  
Vol 35 (43) ◽  
pp. 5932-5938 ◽  
Author(s):  
Lijun Mo ◽  
Qianmei Chen ◽  
Xinji Zhang ◽  
Xiaojun Shi ◽  
Lili Wei ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Tumor Cell ◽  
Tumor Immunity ◽  
Cell Vaccine ◽  
Tumor Cell Vaccine

scholarly journals Leukocyte Counts and T Cell Frequencies Differ Between Novel Subgroups of Diabetes and Associate with Metabolic Parameters and Biomarkers of Inflammation

2021 ◽  
Author(s):  
Jacqueline M. Ratter-Rieck ◽  
Haifa Maalmi ◽  
Sandra Trenkamp ◽  
Oana-Patricia Zaharia ◽  
Wolfgang Rathmann ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Immune Cell ◽  
Autoimmune Diabetes ◽  
Cell Types ◽  
Recent Onset ◽  
Insulin Resistant ◽  
Cell Counts ◽  
Age Related

Frequencies of circulating immune cells are altered in type 1 and type 2 diabetes compared with healthy individuals and associate with insulin sensitivity, glycemic control and lipid levels. This study aimed to determine whether specific immune cell types are associated with novel diabetes subgroups. We analyzed automated white blood cell counts (n=669) and flow cytometry data (n=201) of participants of the German Diabetes Study with recent-onset (<1 year) diabetes, who were allocated to five subgroups based on data-driven analysis of clinical variables. Leukocyte numbers were highest in severe insulin-resistant diabetes (SIRD) and moderate obesity-related diabetes (MOD) and lowest in severe autoimmune diabetes (SAID). CD4<sup>+</sup> T cell frequencies were higher in SIRD vs. SAID, MOD and mild age-related diabetes (MARD), and frequencies of CCR4<sup>+</sup> regulatory T cells were higher in SIRD vs. SAID and MOD and MARD vs. SAID. Pairwise differences between subgroups were partially explained by differences in clustering variables. Frequencies of CD4<sup>+</sup> T cells were positively associated with age, BMI, HOMA2-B and HOMA2-IR, and frequencies of CCR4<sup>+</sup> regulatory T cells with age, HOMA2-B and HOMA2-IR. In conclusion, different leukocyte profiles exist between novel diabetes subgroups and suggest distinct inflammatory processes in these diabetes subgroups.

UP-02.085 Antigen-Specific T-Cell Responses Against Tumor-Antigens Are Controlled by Regulatory T-Cells in Prostate Cancer Patients

Urology ◽  
2011 ◽  
Vol 78 (3) ◽  
pp. S289
Author(s):  
B. Hadaschik ◽  
Y. Su ◽  
E. Hadaschik ◽  
M. Hohenfellner ◽  
P. Beckhove
Keyword(s):  
Prostate Cancer ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cancer Patients ◽  
Tumor Antigens ◽  
T Cell Responses ◽  
Cell Responses

889 ANTIGEN-SPECIFIC T CELL RESPONSES AGAINST TUMOR-ANTIGENS ARE CONTROLLED BY REGULATORY T CELLS IN PROSTATE CANCER PATIENTS

2011 ◽  
Vol 185 (4S) ◽  
Author(s):  
Boris Hadaschik ◽  
Yun Su ◽  
Eva Hadaschik ◽  
Markus Hohenfellner ◽  
Philipp Beckhove
Keyword(s):  
Prostate Cancer ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cancer Patients ◽  
Tumor Antigens ◽  
T Cell Responses ◽  
Cell Responses

scholarly journals LILRB4 suppresses immunity in solid tumors and is a potential target for immunotherapy

2021 ◽  
Vol 218 (7) ◽  
Author(s):  
Naveen Sharma ◽  
Oluwatomisin T. Atolagbe ◽  
Zhongqi Ge ◽  
James P. Allison
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Immunity ◽  
Cd8 T Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Tumor Burden ◽  
Inhibitory Receptor ◽  
Tumor Challenge ◽  
Cell Ratio

Immune receptors expressed on TAMs are intriguing targets for tumor immunotherapy. In this study, we found inhibitory receptor LILRB4 on a variety of intratumoral immune cell types in murine tumor models and human cancers, most prominently on TAMs. LILRB4, known as gp49B in mice, is a LILRB family receptor. Human and murine LILRB4 have two extracellular domains but differ in the number of intracellular ITIMs (three versus two). We observed a high correlation in LILRB4 expression with other immune inhibitory receptors. After tumor challenge, LILRB4−/− mice and mice treated with anti-LILRB4 antibody showed reduced tumor burden and increased survival. LILRB4−/− genotype or LILRB4 blockade increased tumor immune infiltrates and the effector (Teff) to regulatory (Treg) T cell ratio and modulated phenotypes of TAMs toward less suppressive, CD4+ T cells to Th1 effector, and CD8+ T cells to less exhausted. These findings reveal that LILRB4 strongly suppresses tumor immunity in TME and that alleviating that suppression provides antitumor efficacy.

scholarly journals Immunopathological characteristics of coronavirus disease 2019 cases in Guangzhou, China

2020 ◽  
Author(s):  
Yaling Shi ◽  
Mingkai Tan ◽  
Xing Chen ◽  
Yanxia Liu ◽  
Jide Huang ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Regulatory T Cells ◽  
Hospital Stay ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
Immune Cell ◽  
Length Of Hospital Stay ◽  
Cell Types ◽  
Respiratory Disorder

SummaryCoronavirus disease 2019 (COVID-19) is a respiratory disorder caused by the highly contagious SARS-CoV-2. The immunopathological characteristics of COVID-19 patients, either systemic or local, have not been thoroughly studied. In the present study, we analyzed both the changes in the cellularity of various immune cell types as well as cytokines important for immune reactions and inflammation. Our data indicate that patients with severe COVID-19 exhibited an overall decline of lymphocytes including CD4+ and CD8+ T cells, B cells, and NK cells. The number of immunosuppressive regulatory T cells was moderately increased in patients with mild COVID-19. IL-2, IL-6, and IL-10 were remarkably up-regulated in patients with severe COVID-19. The levels of IL-2 and IL-6 relative to the length of hospital stay underwent a similar “rise-decline”pattern, probably reflecting the therapeutic effect. In conclusion, our study shows that the comprehensive decrease of lymphocytes, and the elevation of IL-2 and IL-6 are reliable indicators of severe COVID-19.

scholarly journals Leukocyte Counts and T Cell Frequencies Differ Between Novel Subgroups of Diabetes and Associate with Metabolic Parameters and Biomarkers of Inflammation

2021 ◽  
Author(s):  
Jacqueline M. Ratter-Rieck ◽  
Haifa Maalmi ◽  
Sandra Trenkamp ◽  
Oana-Patricia Zaharia ◽  
Wolfgang Rathmann ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Immune Cell ◽  
Autoimmune Diabetes ◽  
Cell Types ◽  
Recent Onset ◽  
Insulin Resistant ◽  
Cell Counts ◽  
Age Related

Frequencies of circulating immune cells are altered in type 1 and type 2 diabetes compared with healthy individuals and associate with insulin sensitivity, glycemic control and lipid levels. This study aimed to determine whether specific immune cell types are associated with novel diabetes subgroups. We analyzed automated white blood cell counts (n=669) and flow cytometry data (n=201) of participants of the German Diabetes Study with recent-onset (<1 year) diabetes, who were allocated to five subgroups based on data-driven analysis of clinical variables. Leukocyte numbers were highest in severe insulin-resistant diabetes (SIRD) and moderate obesity-related diabetes (MOD) and lowest in severe autoimmune diabetes (SAID). CD4<sup>+</sup> T cell frequencies were higher in SIRD vs. SAID, MOD and mild age-related diabetes (MARD), and frequencies of CCR4<sup>+</sup> regulatory T cells were higher in SIRD vs. SAID and MOD and MARD vs. SAID. Pairwise differences between subgroups were partially explained by differences in clustering variables. Frequencies of CD4<sup>+</sup> T cells were positively associated with age, BMI, HOMA2-B and HOMA2-IR, and frequencies of CCR4<sup>+</sup> regulatory T cells with age, HOMA2-B and HOMA2-IR. In conclusion, different leukocyte profiles exist between novel diabetes subgroups and suggest distinct inflammatory processes in these diabetes subgroups.

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