scholarly journals P02.08 The role of FoxP3+ regulatory T cells and IDO+ immune and tumor cells in malignant melanoma – an immunohistochemical study

2021 ◽  
Vol 9 (Suppl 1) ◽  
pp. A10.2-A11
Author(s):  
S Salmi ◽  
A Lin ◽  
B Hirschovits-Gerz ◽  
M Valkonen ◽  
N Aaltonen ◽  
...  
Keyword(s):  
T Cells ◽  
Prognostic Factors ◽  
Regulatory T Cells ◽  
Tumor Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Positive Association ◽  
Melanoma Cells ◽  
Cell Counts

BackgroundAlthough Malignant Cutaneous Melanoma (CM) is a highly immunogenic cancer, it can evade the immune system by forming an immunosuppressive tumor microenvironment (TME). FoxP3+ Regulatory T cells (Tregs) and indoleamine-2,3-dioxygenase (IDO) are a part of the immunosuppressive TME in CM. In previous studies, IDO expression correlates with poor prognosis and greater Breslow’s depth, but results concerning the role of FoxP3+ Tregs in CM have been controversial. Furthermore, the correlation between IDO and Tregs has not been substantially studied in CM, although IDO is known to be an important regulator of Tregs activity. To develop new therapeutic strategies, it is important to understand the role of immunosuppressive factors in CM.Materials and MethodsWe investigated the associations of FoxP3+ Tregs, IDO+ tumor cells and IDO+ stromal immune cells with tumor stage, prognostic factors, and survival in CM. FoxP3 and IDO were immunohistochemically stained from 29 benign and 29 dysplastic nevi, 18 in situ -melanomas, 48 superficial and 62 deep melanomas and 67 lymph node metastases of CM. The number of FoxP3+ Tregs and IDO+ stromal immune cells was analysed quantitatively and the coverage and intensity of IDO+ tumor cells was evaluated semiquantitatively. Tumors were divided into IDO-negative and IDO-positive, containing less or more than 1% IDO+ melanoma cells of all tumor cells, respectively. P values equal to or less than 0.05 were considered statistically significant.ResultsIDO+ stromal immune cells and FoxP3+ Tregs mainly accumulated in the areas with lymphocyte infiltration and thus resided mostly in the perilesional stroma. The number of FoxP3+ Tregs and IDO+ stromal immune cells were significantly higher in malignant melanomas compared with benign lesions. The increased expression of IDO in melanoma cells was associated with poor prognostic factors, such as recurrence, nodular growth pattern and increased mitotic count. Furthermore, the expression of IDO in melanoma cells was associated with reduced recurrence-free survival. We further showed that IDO-positive tumors contained significantly higher amounts of FoxP3+ Tregs and IDO+ stromal immune cells than IDO-negative tumors. However, the correlation between FoxP3+ Treg and IDO+ stromal immune cell counts was rather weak.ConclusionsOur results indicate that IDO expression is intimately involved in creating a TME conducive to tumor growth in CM. Thus, targeting IDO enzymatic pathway might be a worth of further studies in CM. Furthermore, we show that FoxP3+ Tregs appear to contribute to the immunosuppressive TME in CM, but their role may not be that critical to melanoma progression. The positive association of FoxP3+ Tregs with IDO+ melanoma cells, but not with IDO+ stromal immune cells, indicates a complex interaction between IDO and Tregs in CM, which demands further studies. Support: Sigrid Juselius Foundation (S.P.-S.), Academy of Finland (S.P.-S.), The Paavo Koistinen Foundation (S.S.), Emil Aaltonen Foundation (S.S.) and North-Savo Cultural Foundation (S.S.).Disclosure InformationS. Salmi: None. A. Lin: None. B. Hirschovits-Gerz: None. M. Valkonen: None. N. Aaltonen: None. R. Sironen: None. H. Siiskonen: None. S. Pasonen-Seppänen: None.

scholarly journals The role of FoxP3+ regulatory T cells and IDO+ immune and tumor cells in malignant melanoma – an immunohistochemical study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Satu Salmi ◽  
Anton Lin ◽  
Benjamin Hirschovits-Gerz ◽  
Mari Valkonen ◽  
Niina Aaltonen ◽  
...  
Keyword(s):  
T Cells ◽  
Prognostic Factors ◽  
Regulatory T Cells ◽  
Tumor Cells ◽  
Immune Cells ◽  
Positive Association ◽  
Tumor Stage ◽  
Melanoma Cells ◽  
Melanoma Progression

Abstract Background FoxP3+ Regulatory T cells (Tregs) and indoleamine-2,3-dioxygenase (IDO) participate in the formation of an immunosuppressive tumor microenvironment (TME) in malignant cutaneous melanoma (CM). Recent studies have reported that IDO expression correlates with poor prognosis and greater Breslow’s depth, but results concerning the role of FoxP3+ Tregs in CM have been controversial. Furthermore, the correlation between IDO and Tregs has not been substantially studied in CM, although IDO is known to be an important regulator of Tregs activity. Methods We investigated the associations of FoxP3+ Tregs, IDO+ tumor cells and IDO+ stromal immune cells with tumor stage, prognostic factors and survival in CM. FoxP3 and IDO were immunohistochemically stained from 29 benign and 29 dysplastic nevi, 18 in situ -melanomas, 48 superficial and 62 deep melanomas and 67 lymph node metastases (LNMs) of CM. The number of FoxP3+ Tregs and IDO+ stromal immune cells, and the coverage and intensity of IDO+ tumor cells were analysed. Results The number of FoxP3+ Tregs and IDO+ stromal immune cells were significantly higher in malignant melanomas compared with benign lesions. The increased expression of IDO in melanoma cells was associated with poor prognostic factors, such as recurrence, nodular growth pattern and increased mitotic count. Furthermore, the expression of IDO in melanoma cells was associated with reduced recurrence˗free survival. We further showed that there was a positive correlation between IDO+ tumor cells and FoxP3+ Tregs. Conclusions These results indicate that IDO is strongly involved in melanoma progression. FoxP3+ Tregs also seems to contribute to the immunosuppressive TME in CM, but their significance in melanoma progression remains unclear. The positive association of FoxP3+ Tregs with IDO+ melanoma cells, but not with IDO+ stromal immune cells, indicates a complex interaction between IDO and Tregs in CM, which demands further studies.

scholarly journals Tumor Immune Microenvironment and Its Related miRNAs in Tumor Progression

2021 ◽  
Vol 12 ◽  
Author(s):  
Yingying Xing ◽  
Guojing Ruan ◽  
Haiwei Ni ◽  
Hai Qin ◽  
Simiao Chen ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Immune Cells ◽  
Suppressor Cells ◽  
Immune Microenvironment ◽  
Non Coding Rna ◽  
Tumor Immune Microenvironment ◽  
Downstream Gene Expression

MiRNA is a type of small non-coding RNA, by regulating downstream gene expression that affects the progression of multiple diseases, especially cancer. MiRNA can participate in the biological processes of tumor, including proliferation, invasion and escape, and exhibit tumor enhancement or inhibition. The tumor immune microenvironment contains numerous immune cells. These cells include lymphocytes with tumor suppressor effects such as CD8+ T cells and natural killer cells, as well as some tumor-promoting cells with immunosuppressive functions, such as regulatory T cells and myeloid-derived suppressor cells. MiRNA can affect the tumor immune microenvironment by regulating the function of immune cells, which in turn modulates the progression of tumor cells. Investigating the role of miRNA in regulating the tumor immune microenvironment will help elucidate the specific mechanisms of interaction between immune cells and tumor cells, and may facilitate the use of miRNA as a predictor of immune disorders in tumor progression. This review summarizes the multifarious roles of miRNA in tumor progression through regulation of the tumor immune microenvironment, and provides guidance for the development of miRNA drugs to treat tumors and for the use of miRNA as an auxiliary means in tumor immunotherapy.

scholarly journals MicroRNAs expression profile in CCR6+ regulatory T cells

2014 ◽  
Author(s):  
Juanjuan Zhao ◽  
Yongju Li ◽  
Yan Hu ◽  
Chao Chen ◽  
Ya Zhou ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Signaling Pathways ◽  
Expression Profile ◽  
Immune Cells ◽  
Potential Role ◽  
Biological Function ◽  
Fold Change ◽  
Insight Into

Backgroud: CCR6+ CD4+ regulatory T cells (CCR6+Tregs), a distinct Tregs subset, played an important role in various immune diseases. Recent evidence showed that microRNAs (miRNAs) are vital regulators in the function of immune cells. However, the potential role of miRNAs in the function of CCR6+Tregs remains largely unknown. In this study, we detected the expression profile of miRNAs in CCR6+ Tregs. Materials and Methods: The expression profile of miRNAs as well as genes in CCR6+Tregs or CCR6-Tregs from Balb/c mice were detected by microarray. The signaling pathways were analyzed using Keggs pathway library. Results: We found that there were 58 miRNAs significantly upregulated and 62 downregulated up to 2 fold in CCR6+Tregs compared with CCR6-Tregs. Moreover, 1391 genes were observed with 3 fold change and 20 signaling pathways were enriched using Keggs pathway library. Conclusion: The present data firstly showed CCR6+Tregs expressed specific miRNAs pattern, which provide an insight into the role of miRNAs in the biological function of distinct Tregs subsets.

scholarly journals MicroRNAs expression profile in CCR6+ regulatory T cells

2014 ◽  
Author(s):  
Juanjuan Zhao ◽  
Yongju Li ◽  
Yan Hu ◽  
Chao Chen ◽  
Ya Zhou ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Signaling Pathways ◽  
Expression Profile ◽  
Immune Cells ◽  
Potential Role ◽  
Biological Function ◽  
Fold Change ◽  
Insight Into

Backgroud: CCR6+ CD4+ regulatory T cells (CCR6+Tregs), a distinct Tregs subset, played an important role in various immune diseases. Recent evidence showed that microRNAs (miRNAs) are vital regulators in the function of immune cells. However, the potential role of miRNAs in the function of CCR6+Tregs remains largely unknown. In this study, we detected the expression profile of miRNAs in CCR6+ Tregs. Materials and Methods: The expression profile of miRNAs as well as genes in CCR6+Tregs or CCR6-Tregs from Balb/c mice were detected by microarray. The signaling pathways were analyzed using Keggs pathway library. Results: We found that there were 58 miRNAs significantly upregulated and 62 downregulated up to 2 fold in CCR6+Tregs compared with CCR6-Tregs. Moreover, 1391 genes were observed with 3 fold change and 20 signaling pathways were enriched using Keggs pathway library. Conclusion: The present data firstly showed CCR6+Tregs expressed specific miRNAs pattern, which provide an insight into the role of miRNAs in the biological function of distinct Tregs subsets.

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.

scholarly journals Common Peripheral Immunity Mechanisms in Multiple Sclerosis and Alzheimer's Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Barbara Rossi ◽  
Bruno Santos-Lima ◽  
Eleonora Terrabuio ◽  
Elena Zenaro ◽  
Gabriela Constantin
Keyword(s):  
Multiple Sclerosis ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
T Cells ◽  
Regulatory T Cells ◽  
Neurodegenerative Diseases ◽  
Adaptive Immunity ◽  
Immune Cells ◽  
Pharmacological Intervention

Neurodegenerative diseases are closely related to inflammatory and autoimmune events, suggesting that the dysregulation of the immune system is a key pathological factor. Both multiple sclerosis (MS) and Alzheimer's disease (AD) are characterized by infiltrating immune cells, activated microglia, astrocyte proliferation, and neuronal damage. Moreover, MS and AD share a common pro-inflammatory signature, characterized by peripheral leukocyte activation and transmigration to the central nervous system (CNS). MS and AD are both characterized by the accumulation of activated neutrophils in the blood, leading to progressive impairment of the blood–brain barrier. Having migrated to the CNS during the early phases of MS and AD, neutrophils promote local inflammation that contributes to pathogenesis and clinical progression. The role of circulating T cells in MS is well-established, whereas the contribution of adaptive immunity to AD pathogenesis and progression is a more recent discovery. Even so, blocking the transmigration of T cells to the CNS can benefit both MS and AD patients, suggesting that common adaptive immunity mechanisms play a detrimental role in each disease. There is also growing evidence that regulatory T cells are beneficial during the initial stages of MS and AD, supporting the link between the modulatory immune compartments and these neurodegenerative disorders. The number of resting regulatory T cells declines in both diseases, indicating a common pathogenic mechanism involving the dysregulation of these cells, although their precise role in the control of neuroinflammation remains unclear. The modulation of leukocyte functions can benefit MS patients, so more insight into the role of peripheral immune cells may reveal new targets for pharmacological intervention in other neuroinflammatory and neurodegenerative diseases, including AD.

scholarly journals Abnormal B-Cell and Tfh-Cell Profiles in Patients With Parkinson Disease

2021 ◽  
Vol 9 (2) ◽  
pp. e1125
Author(s):  
Rui Li ◽  
Thomas Francis Tropea ◽  
Laura Rosa Baratta ◽  
Leah Zuroff ◽  
Maria E. Diaz-Ortiz ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Parkinson Disease ◽  
B Cell ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Ex Vivo ◽  
Cell Counts

Background and ObjectivesThere has been growing interest in potential roles of the immune system in the pathogenesis of Parkinson disease (PD). The aim of the current study was to comprehensively characterize phenotypic and functional profiles of circulating immune cells in patients with PD vs controls.MethodsPeripheral blood was collected from patients with PD and age- and sex-matched neurologically normal controls (NCs) in 2 independent cohorts (discovery and validation). Comprehensive multicolor flow cytometry was performed on whole blood leukocytes and peripheral blood mononuclear cells to characterize different immune subsets and their ex vivo responses.ResultsThe discovery cohort included 17 NCs and 12 participants with PD, and the validation cohort included 18 NCs and 18 participants with PD. Among major immune cell types, B cells appeared to be preferentially affected in PD. Proliferating B cell counts were decreased in patients with PD compared with controls. Proportions of B-cell subsets with regulatory capacity such as transitional B cells were preferentially reduced in the patients with PD, whereas proportions of proinflammatory cytokine-producing B cells increased, resulting in a proinflammatory shift of their B-cell functional cytokine responses. Unsupervised principal component analysis revealed increased expression of TNFα and GM-CSF by both B cells and T cells of patients with PD. In addition, levels of follicular T cells, an important B-cell helper T-cell population, decreased in the patients with PD, correlating with their B-cell abnormality.DiscussionOur findings define a novel signature of peripheral immune cells and implicate aberrant Tfh:B-cell interactions in patients with PD.

MO695THE ASSOCIATION OF CIRCULATING CD14++CD16+ MONOCYTES, NATURAL KILLER CELLS AND REGULATORY T CELLS SUBPOPULATIONS WITH CARDIOVASCULAR DISEASE IN A COHORT OF PERITONEAL DIALYSIS PATIENTS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Anila Duni ◽  
Olga Balafa ◽  
George Vartholomatos ◽  
Margarita Oikonomou ◽  
Paraskevi Tseke ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
T Cells ◽  
Peritoneal Dialysis ◽  
Nk Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Normal Range ◽  
Immune Cell Subsets ◽  
Cell Subpopulations

Abstract Background and Aims Advanced chronic kidney disease (CKD) is characterized by elevated expression of the proinflammatory and pro-atherogenic CD14++CD16+ monocytes subset. The role of lymphocyte subpopulations including natural killer (NK) cells and CD4+CD25+ regulatory T cells (Tregs) in the modulation of inflammation and immunity and subsequent cardiovascular implications have received increasing attention. The role of immune cell subpopulations remains to be determined in peritoneal dialysis (PD) patients. The aim of this pilot study was to investigate potential correlations between blood levels of CD14++CD16+ monocytes, NK cells and Tregs with phenotypes of established cardiovascular disease (CVD), including coronary artery disease (CAD) and heart failure (HF) in a cohort of PD patients. Method 29 stable PD patients (mean age 66.96 years ±14.5, 62% males) were enrolled. Exclusion criteria were a history of malignancy, autoimmune disease, active or chronic infections and a recent (&lt; 3 months) cardiovascular event. Demographic, laboratory and bioimpedance measurements data (overhydration, extracellular and total body water and their ratios) were collected. The analysis of peripheral blood immune cell subsets was performed using flow cytometry (FC). Additionally, in 7 PD patients the distribution of the immune cells was evaluated by FC at two time points: T0 (before initiation of PD - CKD stage G5) and T1 (after PD start). Results The median dialysis vintage was 34.5 (range 3.2-141) months. Overall, PD patients had 527 ± 199 monocytes and 1731 ± 489 lymphocytes while mean percentage of CD14++CD16+ monocytes was 9.3 ±6.36% (normal range 2-8%), NK cells 16.6±10.3% (normal range 5-15%) and Tregs 2.1±1.76% (normal range 1-3%). There was no correlation of either of these cell subpopulations with age, PD vintage, inflammation markers (CRP, fibrinogen, albumin, hsTroponin-I), overhydration markers or comorbidities. Only increased NK cells were associated with the presence of HF in PD (24.87 vs 14.92%, p 0.047). In multiple regression analysis, NK cells levels were strongly associated with the presence of edema (beta coef=13.7, p&lt;0.001) and CAD (beta coef=7.1, p=0.046). At T0 mean percentage of CD14++CD16+ monocytes, NK cells and Tregs were 9.7 ±4.5%, 17.1 ±3.84% and 2.38± 1.26% respectively whereas at T1 mean percentage of CD14++CD16+ monocytes was 13.3% ±8.4, NK cells 19.8±6.47% and Tregs 1.5±0.6%. Paired t-test of cell subpopulations (T0 vs T1) showed that only the Tregs were significantly decreased (p =0.018), while the other subpopulations did not differ and remained increased. Conclusion Our study is the first to evaluate the potential association between specific immune cell subsets and cardiovascular disease in long-term PD patients. Increased NK cells levels directly correlate both with the presence of HF and CAD in PD patients. Longitudinal results suggest that CD14++CD16+ and NK cells remain increased after PD start, while Tregs decrease further. The state of pro-inflammation and immune deregulation appear to persist after initiating PD. Future research is required to evaluate the role of immune cells subsets as potential tools to identify patients who are at the highest risk for complications and to guide interventions that may improve clinical outcomes.

Role of Regulatory T Cells in Infection and Vaccination During Early Infancy

2018 ◽  
Vol 24 (30) ◽  
pp. 3495-3505
Author(s):  
Samanta C. Funes ◽  
Miguel A. Mansilla ◽  
Gisela Canedo-Marroquín ◽  
Margarita K. Lay ◽  
Claudia A. Riedel ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Active Role ◽  
Treg Cells ◽  
Health Goals ◽  
Inhibitory Mechanisms ◽  
Neonates And Infants

Reducing infant mortality due to infectious diseases is one of the most important public health goals worldwide. Several approaches have been implemented to reach this goal and vaccination has been an effective strategy for reducing infant and newborn mortality. However, the immunological features of neonates and infants represent a significant barrier to the effectiveness of vaccination. Since regulatory T cells (Treg cells) are known to play an active role in contributing to various mechanisms of suppression of the immune cell function. It has been proposed that these immune cells could decrease the immunogenicity of vaccines administered in newborns and infants. In this article, we discuss the various types of Treg cells, along with their suppressing and inhibitory mechanisms, which are used by these cells in the context of infectious and immunization processes in newborns and infants.

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