scholarly journals Regulatory T Cells in Human Ovarian Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Dong-Jun Peng ◽  
Rebecca Liu ◽  
Weiping Zou
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Immune Suppression ◽  
Immune Cells ◽  
Clinical Settings ◽  
Human Ovarian Cancer ◽  
Cancer Microenvironment ◽  
Cellular Mechanisms ◽  
And Function ◽  
Antigen Presenting

Multiple layers of suppressive components including regulatory T (TReg) cells, suppressive antigen-presenting cells, and inhibitory cytokines form suppressive networks in the ovarian cancer microenvironment. It has been demonstrated that as a major suppressive element, TRegcells infiltrate tumor, interact with several types of immune cells, and mediate immune suppression through different molecular and cellular mechanisms. In this paper, we focus on human ovarian cancer and will discuss the nature of TRegcells including their subsets, trafficking, expansion, and function. We will briefly review the development of manipulation of TRegcells in preclinical and clinical settings.

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.

scholarly journals The Role of Myeloid-Derived Suppressor Cells (MDSCs) in the Development and/or Progression of Endometriosis-State of the Art

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 677
Author(s):  
Dorota Suszczyk ◽  
Wiktoria Skiba ◽  
Joanna Jakubowicz-Gil ◽  
Jan Kotarski ◽  
Iwona Wertel
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Chronic Inflammation ◽  
Immune Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Immunological Diseases ◽  
Underlying Mechanisms ◽  
And Function ◽  
The Impact

Endometriosis (EMS) is a common gynecological disease characterized by the presence of endometrial tissue outside the uterus. Approximately 10% of women around the world suffer from this disease. Recent studies suggest that endometriosis has potential to transform into endometriosis-associated ovarian cancer (EAOC). Endometriosis is connected with chronic inflammation and changes in the phenotype, activity, and function of immune cells. The underlying mechanisms include quantitative and functional disturbances of neutrophils, monocytes/macrophages (MO/MA), natural killer cells (NK), and T cells. A few reports have shown that immunosuppressive cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) may promote the progression of endometriosis. MDSCs are a heterogeneous population of immature myeloid cells (dendritic cells, granulocytes, and MO/MA precursors), which play an important role in the development of immunological diseases such as chronic inflammation and cancer. The presence of MDSCs in pathological conditions correlates with immunosuppression, angiogenesis, or release of growth factors and cytokines, which promote progression of these diseases. In this paper, we review the impact of MDSCs on different populations of immune cells, focusing on their immunosuppressive role in the immune system, which may be related with the pathogenesis and/or progression of endometriosis and its transformation into ovarian cancer.

scholarly journals CAR T Cells: Cancer Cell Surface Receptors Are the Target for Cancer Therapy

2021 ◽  
Author(s):  
Behrouz Shademan ◽  
Vahidreza Karamad ◽  
Alireza Nourazarian ◽  
Cigir Biray Avcı
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Basic Structure ◽  
Antigen Binding ◽  
Chimeric Receptors ◽  
Surface Receptors ◽  
Car T Cells ◽  
Car T ◽  
And Function ◽  
Antigenic Targets

Immunotherapy has become a prominent strategy for the treatment of cancer. A method that improves the immune system's ability to attack a tumor (Enhances antigen binding). Targeted killing of malignant cells by adoptive transfer of chimeric antigen receptor (CAR) T cells is a promising immunotherapy technique in the treatment of cancers. For this purpose, the patient's immune cells, with genetic engineering aid, are loaded with chimeric receptors that have particular antigen binding and activate cytotoxic T lymphocytes. That increases the effectiveness of immune cells and destroying cancer cells. This review discusses the basic structure and function of CAR-T cells and how antigenic targets are identified to treat different cancers and address the disadvantages of this treatment for cancer.

scholarly journals Age-Related Changes in Thymic Central Tolerance

2021 ◽  
Vol 12 ◽  
Author(s):  
Jayashree Srinivasan ◽  
Jessica N. Lancaster ◽  
Nandini Singarapu ◽  
Laura P. Hale ◽  
Lauren I. R. Ehrlich ◽  
...  
Keyword(s):  
T Cells ◽  
Negative Selection ◽  
Thymic Epithelial Cells ◽  
Central Tolerance ◽  
Adult Transition ◽  
Treg Function ◽  
Age Related ◽  
And Function ◽  
Antigen Presenting ◽  
Age Related Changes

Thymic epithelial cells (TECs) and hematopoietic antigen presenting cells (HAPCs) in the thymus microenvironment provide essential signals to self-reactive thymocytes that induce either negative selection or generation of regulatory T cells (Treg), both of which are required to establish and maintain central tolerance throughout life. HAPCs and TECs are comprised of multiple subsets that play distinct and overlapping roles in central tolerance. Changes that occur in the composition and function of TEC and HAPC subsets across the lifespan have potential consequences for central tolerance. In keeping with this possibility, there are age-associated changes in the cellular composition and function of T cells and Treg. This review summarizes changes in T cell and Treg function during the perinatal to adult transition and in the course of normal aging, and relates these changes to age-associated alterations in thymic HAPC and TEC subsets.

Immune cells of the epithelial ovarian cancer microenvironment

2021 ◽  
pp. 67-78
Author(s):  
Varvara Nikolaevna Zhurman ◽  
Natalia Gennadevna Plekhova ◽  
Ekaterina Valeryevna Eliseeva
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Immune Cells ◽  
Ovarian Tumor ◽  
Biologically Active ◽  
Cancer Microenvironment ◽  
Review Of The Literature ◽  
Prognostic Role ◽  
Active Substances

The article is a review of the literature, which analyzes the data on the role of cells of the immune system, cytokines and other biologically active substances secreted by them in the interstitial space of an ovarian tumor. The emphasis is made on the mechanism of realization by immune cells of the stimulating and suppressing action on the development of the tumor. Considerable attention is paid to the prognostic role of immune cells in the development of epithelial ovarian cancer.

scholarly journals The Role of HLA-G in Tumor Escape: Manipulating the Phenotype and Function of Immune Cells

2020 ◽  
Vol 10 ◽  
Author(s):  
Lu Liu ◽  
Lijun Wang ◽  
Lihong Zhao ◽  
Chen He ◽  
Ganlu Wang
Keyword(s):  
T Cells ◽  
Tumor Immunity ◽  
Immune Cells ◽  
Human Leukocyte ◽  
Therapeutic Benefit ◽  
Tumor Escape ◽  
Class I Mhc ◽  
Mhc I ◽  
Suppressive Phenotype ◽  
And Function

Human leukocyte antigen-G (HLA-G) is a non-classical major histocompatibility complex class I (MHC I) molecule, and under physiological conditions, its expression is strictly restricted to the maternal–fetal interface and immune-privileged organs where HLA-G is expected to contribute to establishment and maintenance of immune tolerance. However, the expression of HLA-G has been found in various types of tumors, and the level of its expression frequently correlates with high-grade histology and poor prognosis, raising the possibility that it may play a negative role in tumor immunity. ILT2 and ILT4, present on a broad of immune cells, have been identified as the main receptors engaging HLA-G, and their interactions have been found to allow the conversion of effectors like NK cells and T cells to anergic or unresponsive state, activated DCs to tolerogenic state, and to drive the differentiation of T cells toward suppressive phenotype. Therefore, tumors can employ HLA-G to modulate the phenotype and function of immune cells, allowing them to escape immune attack. In this review, we discuss the mechanism underlying HLA-G expression and function, its role played in each step of the tumor-immunity cycle, as well as the potential to target it for therapeutic benefit.

Dynamics of T-cell infiltration during the course of ovarian cancer: The gradual shift from a Th17 effector cell response to a predominant infiltration by regulatory T cells.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22129-e22129
Author(s):  
Simona Partlova ◽  
Anna Fialova ◽  
Ludek Sojka ◽  
Lukas Rob ◽  
Jirina Bartunkova ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Culture ◽  
Flow Cytometry ◽  
T Cells ◽  
Regulatory T Cells ◽  
Tumor Cell ◽  
Immune Cells ◽  
Tumor Tissue ◽  
Tumor Cell Culture ◽  
Culture Supernatants

e22129 Background: Ovarian cancer is diagnosed in more than 190,000 new patients every year and is known to have the highest mortality rate among gynaecologic cancers. The type of immune cells that are present within the tumor microenvironment can play a crucial role in the survival of patients. However, little is known about the dynamics of the tumor-infiltrating immune cells during disease progression. Methods: We studied the immune cells infiltrating the tumor tissue of ovarian cancer patients at different stages of disease. We analysed the patterns of T lymphocytes in fresh tumor tissue as well as blood samples of 44 newly diagnosed ovarian cancer patients by flow cytometry. To evaluate whether regulatory T cells (Tregs) develop in situ or migrate to tumor tissue, we measured a concentration of chemokine CCL22 in tumor cell culture supernatants. We also determined the expression of CCR4 on circulating as well as tumor-infiltrating Tregs by flow cytometry. Results: The early stages of development of ovarian carcinomas were characterized by a strong Th17 immune response, whereas in stage II patients, recruitment of high numbers of Th1 cells was observed. In disseminated tumors (stage III-IV), we detected a dominant population of Helios+ activated regulatory T cells along with high numbers of macrophages and immature myeloid dendritic cells. Tumor-infiltrating Tregs had markedly lower expression of CCR4 than circulating Tregs, and the numbers of tumor-infiltrating Tregs significantly correlated with the levels of CCL22 in ovarian tumor cell culture supernatants, suggesting their recruitment via a CCR4/CCL22 interaction. CCL22 was mainly produced by tumor cells, macrophages and mDCs in the primary ovarian tumors, and its expression markedly increased in response to IFNgamma. Conclusions: Taken together, the specific recruitment of Tregs, probably triggered by inflammatory stimuli, leads to a significant immune suppression in the advanced stages of ovarian cancer.

Adhesion of human T cells to antigen-presenting cells through SIRPβ2-CD47 interaction costimulates T-cell proliferation

Blood ◽  
2005 ◽  
Vol 105 (6) ◽  
pp. 2421-2427 ◽  
Author(s):  
Laura Piccio ◽  
William Vermi ◽  
Kent S. Boles ◽  
Anja Fuchs ◽  
Carey A. Strader ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Antigen Presenting Cells ◽  
Cell Types ◽  
Orphan Receptor ◽  
T Cell Proliferation ◽  
Central Nervous Systems ◽  
And Function ◽  
Antigen Presenting

AbstractSignal-regulatory proteins (SIRPs) are transmembrane glycoproteins belonging to the immunoglobulin (Ig) superfamily that are expressed in the immune and central nervous systems. SIRPα binds CD47 and inhibits the function of macrophages, dendritic cells, and granulocytes, whereas SIRPβ1 is an orphan receptor that activates the same cell types. A recently identified third member of the SIRP family, SIRPβ2, is as yet uncharacterized in terms of expression, specificity, and function. Here, we show that SIRPβ2 is expressed on T cells and activated natural killer (NK) cells and, like SIRPα, binds CD47, mediating cell-cell adhesion. Consequently, engagement of SIRPβ2 on T cells by CD47 on antigen-presenting cells results in enhanced antigen-specific T-cell proliferation.

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