scholarly journals The Role of Stroma in Cholangiocarcinoma: The Intriguing Interplay between Fibroblastic Component, Immune Cell Subsets and Tumor Epithelium

2018 ◽  
Vol 19 (10) ◽  
pp. 2885 ◽  
Author(s):  
Alessandra Gentilini ◽  
Mirella Pastore ◽  
Fabio Marra ◽  
Chiara Raggi
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Critical Role ◽  
Tumor Stroma ◽  
Typical Feature ◽  
Poor Clinical Outcome ◽  
Soluble Factors ◽  
Secreted Factors ◽  
Immune Cell Subsets

Cholangiocarcinoma (CCA) is a severe and mostly intractable adenocarcinoma of biliary epithelial cells. A typical feature of CCA is its highly desmoplastic microenvironment containing fibrogenic connective tissue and an abundance of immune cells (T lymphocytes, Natural Killer (NK) cells, and macrophages) infiltrating tumor epithelium. This strong desmoplasia is orchestrated by various soluble factors and signals, suggesting a critical role in shaping a tumor growth-permissive microenvironment that is responsible for CCA poor clinical outcome. Indeed stroma not only provides an abundance of factors that facilitate CCA initiation, growth and progression, but also a prejudicial impact on therapeutic outcome. This review will give an overview of tumor-stroma signaling in a microenvironment critically regulating CCA development and progression. Identification of CCA secreted factors by both the fibroblast component and immune cell subsets might provide ample opportunities for pharmacological targeting of this type of cancer.

scholarly journals Tuning cancer fate: the unremitting role of host immunity

Open Biology ◽  
2017 ◽  
Vol 7 (4) ◽  
pp. 170006 ◽  
Author(s):  
B. Calì ◽  
B. Molon ◽  
A. Viola
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Tumour Progression ◽  
Host Immunity ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Immune Mediated ◽  
Immune Cell Subsets ◽  
Therapeutic Protocols

Host immunity plays a central and complex role in dictating tumour progression. Solid tumours are commonly infiltrated by a large number of immune cells that dynamically interact with the surrounding microenvironment. At first, innate and adaptive immune cells successfully cooperate to eradicate microcolonies of transformed cells. Concomitantly, surviving tumour clones start to proliferate and harness immune responses by specifically hijacking anti-tumour effector mechanisms and fostering the accumulation of immunosuppressive immune cell subsets at the tumour site. This pliable interplay between immune and malignant cells is a relentless process that has been concisely organized in three different phases: elimination, equilibrium and escape. In this review, we aim to depict the distinct immune cell subsets and immune-mediated responses characterizing the tumour landscape throughout the three interconnected phases. Importantly, the identification of key immune players and molecules involved in the dynamic crosstalk between tumour and immune system has been crucial for the introduction of reliable prognostic factors and effective therapeutic protocols against cancers.

scholarly journals MMP1, MMP9, and COX2 Expressions in Promonocytes Are Induced by Breast Cancer Cells and Correlate with Collagen Degradation, Transformation-Like Morphological Changes in MCF-10A Acini, and Tumor Aggressiveness

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
G. K. Chimal-Ramírez ◽  
N. A. Espinoza-Sánchez ◽  
D. Utrera-Barillas ◽  
L. Benítez-Bribiesca ◽  
J. R. Velázquez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Immune Cells ◽  
Immune Cell ◽  
Morphological Changes ◽  
Tumor Stroma ◽  
Collagen Degradation ◽  
Tumor Aggressiveness ◽  
Soluble Factors ◽  
Immune Effector

Tumor-associated immune cells often lack immune effector activities, and instead they present protumoral functions. To understand how tumors promote this immunological switch, invasive and noninvasive breast cancer cell (BRC) lines were cocultured with a promonocytic cell line in a Matrigel-based 3D system. We hypothesized that if communication exists between tumor and immune cells, coculturing would result in augmented expression of genes associated with tumor malignancy. Upregulation of proteasesMMP1andMMP9and inflammatoryCOX2genes was found likely in response to soluble factors. Interestingly, changes were more apparent in promonocytes and correlated with the aggressiveness of the BRC line. Increased gene expression was confirmed by collagen degradation assays and immunocytochemistry of prostaglandin 2, a product of COX2 activity. Untransformed MCF-10A cells were then used as a sensor of soluble factors with transformation-like capabilities, finding that acini formed in the presence of supernatants of the highly aggressive BRC/promonocyte cocultures often exhibited total loss of the normal architecture. These data support that tumor cells can modify immune cell gene expression and tumor aggressiveness may importantly reside in this capacity. Modeling interactions in the tumor stroma will allow the identification of genes useful as cancer prognostic markers and therapy targets.

The role of SLAM family receptors in immune cell signalingThis paper is one of a selection of papers published in this Special Issue, entitled CSBMCB — Membrane Proteins in Health and Disease.

2006 ◽  
Vol 84 (6) ◽  
pp. 832-843 ◽  
Author(s):  
Elena A. Ostrakhovitch ◽  
Shawn S.-C. Li
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Current Knowledge ◽  
Critical Role ◽  
Cell Types ◽  
Health And Disease ◽  
Slam Family ◽  
Different Cell Types ◽  
Selection Of

The signaling lymphocyte-activating molecule (SLAM) family immunoreceptors are expressed in a wide array of immune cells, including both T and B lymphocytes. By virtue of their ability to transduce tyrosine phosphorylation signals through the so-called ITSM (immunoreceptor tyrosine-based switch motif) sequences, they play an important part in regulating both innate and adaptive immune responses. The critical role of the SLAM immunoreceptors in mediating normal immune reactions was highlighted in recent findings that SAP, a SLAM-associated protein, modulates the activities of various immune cells through interactions with different members of the SLAM family expressed in these cells. Importantly, mutations or deletions of the sap gene in humans result in the X-linked lymphoproliferative syndrome. In this review, we summarize current knowledge and survey the latest developments in signal transduction events triggered by the activation of SLAM family receptors in different cell types.

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 (< 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<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.

Abstract 175: The Role of Axl in Accumulation of Immune Cells in Kidney and the Onset of Hypertension

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Sri Nagarjun Batchu ◽  
Angie Hughson ◽  
Janice Gerloff ◽  
Deborah J Fowell ◽  
Vyacheslav A Korshunov
Keyword(s):  
Blood Pressure ◽  
Immune Cells ◽  
Immune Cell ◽  
Kidney Injury ◽  
Wild Type ◽  
Protein Levels ◽  
Immune Cell Subsets ◽  
Early Increase ◽  
Salt Hypertension

Introduction: Gas6/Axl pathway contributes to elevation of blood pressure. Immune cells are implicated in initiation and maintenance of hypertension. In this study we aimed to investigate the role of Axl in immune cells on kidney injury and initiation of hypertension. Methods and Results: Deoxycorticosterone-acetate (DOCA; 75mg, 60days release) and salt hypertension was induced for 1wk or 6wks in four groups of Axl chimeras (n=4-5) that were generated by bone marrow (BM) transplant. Multi parameter flow cytometry was used to quantify five major immune cell subsets in digested kidneys from Axl chimeras. Systolic blood pressure (SBP) increased by 30mmHg in Axl+/+ →Axl+/+, Axl-/- →Axl-/- and Axl+/+ →Axl-/- mice after 1wk of DOCA-salt. However, chimeras that lack Axl in the BM cells (Axl-/- →Axl+/+) showed reduction in early increase in SBP (16+2mmHg). We observed a significant decrease in urine protein levels in Axl-/- →Axl+/+ (0.3+0.1μg/μl) compared to other Axl chimeras (∼0.7μg/μl) after 1wk of DOCA-salt. Kidney glomeruli areas were reduced in Axl-/- →Axl+/+ (4,143+229μm 2 ) compared to other Axl chimeras (∼6,000μm 2 ) after 6wks of DOCA-salt. Kidneys from Axl-/- →Axl-/- showed an increase in total leukocytes (8 vs. 4%), B cells (29 vs. 12%) and decrease in monocytes/macrophages (16 vs. 22%) and dendritic cells (5 vs. 10%) compared to Axl+/+ →Axl+/+. Moreover, Axl-/- →Axl+/+ showed further increase in leukocytes (17%), B (39%) and dendritic (13%) cells in kidneys compared to other Axl chimeras. In addition a small percentage of wild type T cells was increased in the kidneys from Axl-/- →Axl+/+ chimeras. Conclusions: These findings suggest that Axl expression in BM-derived cells is critical for kidney injury in DOCA-salt hypertension. Axl-dependent pathways regulate immune cell populations in the kidneys during initiation of hypertension. This study was supported by HL105623 grant (VAK)

scholarly journals Peripheral immune cells and perinatal brain injury: a double-edged sword?

2021 ◽  
Author(s):  
Josephine Herz ◽  
Ivo Bendix ◽  
Ursula Felderhoff-Müser
Keyword(s):  
Brain Injury ◽  
Immune Cells ◽  
Drug Exposure ◽  
Immune Cell ◽  
List Type ◽  
Perinatal Brain Injury ◽  
Immune Cell Subsets ◽  
Peripheral Immune Cells ◽  
Critical Aspects

Abstract Perinatal brain injury is the leading cause of neurological mortality and morbidity in childhood ranging from motor and cognitive impairment to behavioural and neuropsychiatric disorders. Various noxious stimuli, including perinatal inflammation, chronic and acute hypoxia, hyperoxia, stress and drug exposure contribute to the pathogenesis. Among a variety of pathological phenomena, the unique developing immune system plays an important role in the understanding of mechanisms of injury to the immature brain. Neuroinflammation following a perinatal insult largely contributes to evolution of damage to resident brain cells, but may also be beneficial for repair activities. The present review will focus on the role of peripheral immune cells and discuss processes involved in neuroinflammation under two frequent perinatal conditions, systemic infection/inflammation associated with encephalopathy of prematurity (EoP) and hypoxia/ischaemia in the context of neonatal encephalopathy (NE) and stroke at term. Different immune cell subsets in perinatal brain injury including their infiltration routes will be reviewed and critical aspects such as sex differences and maturational stage will be discussed. Interactions with existing regenerative therapies such as stem cells and also potentials to develop novel immunomodulatory targets are considered. Impact Comprehensive summary of current knowledge on the role of different immune cell subsets in perinatal brain injury including discussion of critical aspects to be considered for development of immunomodulatory therapies.

scholarly journals The Role of the Bone Marrow Microenvironment in the Response to Infection

2020 ◽  
Vol 11 ◽  
Author(s):  
Courtney B. Johnson ◽  
Jizhou Zhang ◽  
Daniel Lucas
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Immune Cells ◽  
Critical Role ◽  
Primary Source ◽  
Bone Marrow Microenvironment ◽  
Future Research ◽  
Multipotent Stem Cells ◽  
Hematopoietic Stem

Hematopoiesis in the bone marrow (BM) is the primary source of immune cells. Hematopoiesis is regulated by a diverse cellular microenvironment that supports stepwise differentiation of multipotent stem cells and progenitors into mature blood cells. Blood cell production is not static and the bone marrow has evolved to sense and respond to infection by rapidly generating immune cells that are quickly released into the circulation to replenish those that are consumed in the periphery. Unfortunately, infection also has deleterious effects injuring hematopoietic stem cells (HSC), inefficient hematopoiesis, and remodeling and destruction of the microenvironment. Despite its central role in immunity, the role of the microenvironment in the response to infection has not been systematically investigated. Here we summarize the key experimental evidence demonstrating a critical role of the bone marrow microenvironment in orchestrating the bone marrow response to infection and discuss areas of future research.

scholarly journals Emerging Role of Exosomes in Tuberculosis: From Immunity Regulations to Vaccine and Immunotherapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Yin-Fu Sun ◽  
Jiang Pi ◽  
Jun-Fa Xu
Keyword(s):  
Immune Responses ◽  
Delivery System ◽  
Immune Modulation ◽  
Immune Cell ◽  
Critical Role ◽  
Cell Communication ◽  
Immune Defense ◽  
Research Progress ◽  
Recent Research Progress

Exosomes are cell-derived nanovesicles carrying protein, lipid, and nucleic acid for secreting cells, and act as significant signal transport vectors for cell-cell communication and immune modulation. Immune-cell-derived exosomes have been found to contain molecules involved in immunological pathways, such as MHCII, cytokines, and pathogenic antigens. Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains one of the most fatal infectious diseases. The pathogen for tuberculosis escapes the immune defense and continues to replicate despite rigorous and complicate host cell mechanisms. The infected-cell-derived exosomes under this circumstance are found to trigger different immune responses, such as inflammation, antigen presentation, and activate subsequent pathways, highlighting the critical role of exosomes in anti-MTB immune response. Additionally, as a novel kind of delivery system, exosomes show potential in developing new vaccination and treatment of tuberculosis. We here summarize recent research progress regarding exosomes in the immune environment during MTB infection, and further discuss the potential of exosomes as delivery system for novel anti-MTB vaccines and therapies.

scholarly journals Immune cell-specific Cre reporter mouse labels a subset of CNS neurons

2019 ◽  
Author(s):  
Aurélie Bouteau ◽  
Botond Z. Igyártó
Keyword(s):  
Immune Cells ◽  
Langerhans Cells ◽  
Immune Cell ◽  
Neuronal Marker ◽  
Reporter Mouse ◽  
Cns Neurons ◽  
The Central Nervous System ◽  
Antigen Presenting

AbstractHuLangerin-Cre-YFPf/f mice were generated to specifically mark a subset of antigen presenting immune cells, called Langerhans cells (LCs). During histological characterization of these mice, we found that, in addition to LCs an uncharacterized cell population in the central nervous system (CNS) also expressed YFP. In this study, we found that the CNS YFP+ cells were negative for microglia and astrocyte markers, but they expressed mature neuronal marker NeuN and showed neuronal localization/morphology. Thus, these mice might be used to study the ontogeny, migration and the role of a subset of CNS neurons.

Sign in / Sign up

Export Citation Format

Share Document