scholarly journals Human regulatory T cells at the maternal-fetal interface show functional site-specific adaptation with tumor-infiltrating-like features

2019 ◽  
Author(s):  
Judith Wienke ◽  
Laura Brouwers ◽  
Leone van der Burg ◽  
Michal Mokry ◽  
Rianne C. Scholman ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Human Tumor ◽  
Control Site ◽  
Transcriptional Profile ◽  
Functional Adaptation ◽  
Immune Checkpoints ◽  
Site Specific ◽  
Transcriptional Signature ◽  
Maternal Fetal Interface

AbstractObjectivesRegulatory T cells (Tregs) are crucial for maintaining immune tolerance against the semi-allogeneic fetus during pregnancy. Since their functional profile at the human maternal-fetal interface is still elusive, we investigated the transcriptional profile and functional adaptation of human uterine Tregs (uTregs) during pregnancy.MethodsBlood and uterine biopsies from the placental bed (=maternal-fetal interface) and incision site (=control), were obtained from women with uneventful pregnancies undergoing primary Caesarean section. Tregs and CD4+ non-Tregs (Tconv) were isolated for transcriptomic profiling by Cel-Seq2. Results were validated on protein and single cell level by flow cytometry.ResultsPlacental bed uterine Tregs (uTregs) showed elevated expression of Treg signature markers compared to blood Tregs, including FOXP3, CTLA4 and TIGIT. The uTreg transcriptional profile was indicative of late-stage effector Treg differentiation and chronic activation with high expression of immune checkpoints GITR, TNFR2, OX-40, 4-1BB, genes associated with suppressive capacity (CTLA4, HAVCR2, IL10, IL2RA, LAYN, PDCD1), activation (HLA-DR, LRRC32), and transcription factors MAF, PRDM1, BATF, and VDR. uTregs mirrored uTconv Th1 polarization, and characteristics indicating tissue-residency, including high CD69, CCR1, and CXCR6. The particular transcriptional signature of placental bed uTregs overlapped strongly with the specialized profile of human tumor-infiltrating Tregs, and, remarkably, was more pronounced at the placental bed than uterine control site.ConclusionuTregs at the maternal-fetal interface acquire a highly differentiated effector Treg profile similar to tumor-infiltrating Tregs, which is locally enriched compared to a distant uterine site. This introduces the novel concept of site-specific transcriptional adaptation of human Tregs within one organ.

scholarly journals Alterations in regulatory T cells and immune checkpoint molecules in pancreatic cancer patients receiving FOLFIRINOX or gemcitabine plus nab-paclitaxel

2021 ◽  
Author(s):  
L. Sams ◽  
S. Kruger ◽  
V. Heinemann ◽  
D. Bararia ◽  
S. Haebe ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cd8 T Cells ◽  
Mononuclear Cells ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
Immune Checkpoints ◽  
Prognostic Information ◽  
Peripheral Blood Mononuclear

Abstract Purpose This pilot study aimed on generating insight on alterations in circulating immune cells during the use of FOLFIRINOX and gemcitabine/nab-paclitaxel in pancreatic ductal adenocarcinoma (PDAC). Patients and methods Peripheral blood mononuclear cells were isolated before and 30 days after initiation of chemotherapy from 20 patients with advanced PDAC. Regulatory T cells (FoxP3+) and immune checkpoints (PD-1 and TIM-3) were analyzed by flow cytometry and immunological changes were correlated with clinical outcome. Results Heterogeneous changes during chemotherapy were observed in circulating T-cell subpopulations with a pronounced effect on PD-1+ CD4+/CD8+ T cells. An increase in FoxP3+ or PD-1+ T cells had no significant effect on survival. An increase in TIM3+/CD8+ (but not TIM3+/CD4+) T cells was associated with a significant inferior outcome: median progression-free survival in the subgroup with an increase of TIM-3+/CD8+ T cells was 6.0 compared to 14.0 months in patients with a decrease/no change (p = 0.026); corresponding median overall survival was 13.0 and 20.0 months (p = 0.011), respectively. Conclusions Chemotherapy with FOLFIRNOX or gemcitabine/nab-paclitaxel induces variable changes in circulating T-cell populations that may provide prognostic information in PDAC.

scholarly journals FOXP3 Defines Regulatory T Cells in Human Tumor and Autoimmune Disease

2009 ◽  
Vol 69 (9) ◽  
pp. 3995-4000 ◽  
Author(s):  
Ilona Kryczek ◽  
Rebecca Liu ◽  
Guobin Wang ◽  
Ke Wu ◽  
Xiaogong Shu ◽  
...  
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
Regulatory T Cells ◽  
Human Tumor

scholarly journals A multiply redundant genetic switch 'locks in' the transcriptional signature of regulatory T cells

2012 ◽  
Vol 13 (10) ◽  
pp. 972-980 ◽  
Author(s):  
Wenxian Fu ◽  
Ayla Ergun ◽  
Ting Lu ◽  
Jonathan A Hill ◽  
Sokol Haxhinasto ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Genetic Switch ◽  
Transcriptional Signature

scholarly journals Tilting the Balance: Therapeutic Prospects of CD83 as a Checkpoint Molecule Controlling Resolution of Inflammation

2022 ◽  
Vol 23 (2) ◽  
pp. 732
Author(s):  
Katrin Peckert-Maier ◽  
Dmytro Royzman ◽  
Pia Langguth ◽  
Anita Marosan ◽  
Astrid Strack ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Transplant Rejection ◽  
Immune Checkpoints ◽  
Potential Candidate ◽  
Resolution Of Inflammation ◽  
Checkpoint Molecule

Chronic inflammatory diseases and transplant rejection represent major challenges for modern health care. Thus, identification of immune checkpoints that contribute to resolution of inflammation is key to developing novel therapeutic agents for those conditions. In recent years, the CD83 (cluster of differentiation 83) protein has emerged as an interesting potential candidate for such a “pro-resolution” therapy. This molecule occurs in a membrane-bound and a soluble isoform (mCD83 and sCD83, respectively), both of which are involved in resolution of inflammation. Originally described as a maturation marker on dendritic cells (DCs), mCD83 is also expressed by activated B and T cells as well as regulatory T cells (Tregs) and controls turnover of MHC II molecules in the thymus, and thereby positive selection of CD4+ T cells. Additionally, it serves to confine overshooting (auto-)immune responses. Consequently, animals with a conditional deletion of CD83 in DCs or regulatory T cells suffer from impaired resolution of inflammation. Pro-resolving effects of sCD83 became evident in pre-clinical autoimmune and transplantation models, where application of sCD83 reduced disease symptoms and enhanced allograft survival, respectively. Here, we summarize recent advances regarding CD83-mediated resolution of inflammatory responses, its binding partners as well as induced signaling pathways, and emphasize its therapeutic potential for future clinical trials.

scholarly journals Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments

Blood ◽  
2009 ◽  
Vol 114 (6) ◽  
pp. 1141-1149 ◽  
Author(s):  
Ilona Kryczek ◽  
Mousumi Banerjee ◽  
Pui Cheng ◽  
Linhua Vatan ◽  
Wojciech Szeliga ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Regulatory T Cells ◽  
Cancer Patients ◽  
Th17 Cells ◽  
Human Tumor ◽  
Active Role ◽  
Effector T Cells ◽  
Cell Phenotype ◽  
Effector Cells

Abstract Th17 cells play an active role in autoimmune diseases. However, the nature of Th17 cells is poorly understood in cancer patients. We studied Th17 cells, the associated mechanisms, and clinical significance in 201 ovarian cancer patients. Tumor-infiltrating Th17 cells exhibit a polyfunctional effector T-cell phenotype, are positively associated with effector cells, and are negatively associated with tumor-infiltrating regulatory T cells. Tumor-associated macrophages promote Th17 cells through interleukin-1β (IL-1β), whereas tumor-infiltrating regulatory T cells inhibit Th17 cells through an adenosinergic pathway. Furthermore, through synergistic action between IL-17 and interferon-γ, Th17 cells stimulate CXCL9 and CXCL10 production to recruit effector T cells to the tumor microenvironment. The levels of CXCL9 and CXCL10 are associated with tumor-infiltrating effector T cells. The levels of tumor-infiltrating Th17 cells and the levels of ascites IL-17 are reduced in more advanced diseases and positively predict patient outcome. Altogether, Th17 cells may contribute to protective human tumor immunity through inducing Th1-type chemokines and recruiting effector cells to the tumor microenvironment. Inhibition of Th17 cells represents a novel immune evasion mechanism. This study thus provides scientific and clinical rationale for developing novel immune-boosting strategies based on promoting the Th17 cell population in cancer patients.

scholarly journals Human Tumor Antigens and Cancer Immunotherapy

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Nathalie Vigneron
Keyword(s):  
T Cells ◽  
Turning Point ◽  
Tumor Antigens ◽  
Human Tumor ◽  
Immune Checkpoints ◽  
Antigenic Peptides ◽  
Cytolytic T Lymphocytes ◽  
Cell Therapies ◽  
Key Players ◽  
Recent Developments

With the recent developments of adoptive T cell therapies and the use of new monoclonal antibodies against the immune checkpoints, immunotherapy is at a turning point. Key players for the success of these therapies are the cytolytic T lymphocytes, which are a subset of T cells able to recognize and kill tumor cells. Here, I review the nature of the antigenic peptides recognized by these T cells and the processes involved in their presentation. I discuss the importance of understanding how each antigenic peptide is processed in the context of immunotherapy and vaccine delivery.

Blockade of CD86 Signaling Facilitates a Th2 Bias at the Maternal-Fetal Interface and Expands Peripheral CD4+CD25+ Regulatory T Cells to Rescue Abortion-Prone Fetuses1

2005 ◽  
Vol 72 (2) ◽  
pp. 338-345 ◽  
Author(s):  
Xiao-Yong Zhu ◽  
Yue-Hua Zhou ◽  
Ming-Yan Wang ◽  
Li-Ping Jin ◽  
Min-Min Yuan ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Maternal Fetal Interface

scholarly journals Immune Checkpoints Contribute Corneal Immune Privilege: Implications for Dry Eye Associated with Checkpoint Inhibitors

2020 ◽  
Vol 21 (11) ◽  
pp. 3962
Author(s):  
Junko Hori ◽  
Tomoyuki Kunishige ◽  
Yuji Nakano
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Dry Eye ◽  
Molecular Mechanisms ◽  
Checkpoint Inhibitors ◽  
Corneal Transplantation ◽  
Immune Privilege ◽  
Immune Checkpoints ◽  
Corneal Tissue ◽  
Immunosuppressive Microenvironment

The eye is provided with immune protection against pathogens in a manner that greatly reduces the threat of inflammation-induced vision loss. Immune-mediated inflammation and allograft rejection are greatly reduced in the eye, a phenomenon called ‘immune privilege’. Corneal tissue has inherent immune privilege properties with underlying three mechanisms: (1) anatomical, cellular, and molecular barriers in the cornea; (2) an immunosuppressive microenvironment; and (3) tolerance related to regulatory T cells and anterior chamber-associated immune deviation. This review describes the molecular mechanisms of the immunosuppressive microenvironment and regulatory T cells in the cornea that have been elucidated from animal models of ocular inflammation, especially those involving corneal transplantation, it also provides an update on immune checkpoint molecules in corneal and systemic immune regulation, and its relevance for dry eye associated with checkpoint inhibitor therapy.

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