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Article ; Online: Role of TRAFs in Signaling Pathways Controlling T Follicular Helper Cell Differentiation and T Cell-Dependent Antibody Responses.

Pedros, Christophe / Altman, Amnon / Kong, Kok-Fai

2018 Volume 9, Page(s) 2412

Abstract: Follicular helper T ( ... ...

Abstract	Follicular helper T (T
MeSH term(s)	Animals ; Antibody Formation/immunology ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; Cell Communication/immunology ; Cell Differentiation/immunology ; Cytokines/metabolism ; Humans ; Lymphocyte Activation ; NF-kappa B/metabolism ; Signal Transduction ; T-Lymphocytes, Helper-Inducer/cytology ; T-Lymphocytes, Helper-Inducer/immunology ; T-Lymphocytes, Helper-Inducer/metabolism ; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/metabolism
Chemical Substances	Cytokines ; NF-kappa B ; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Language	English
Publishing date	2018-10-22
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2018.02412
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Article ; Online: Protein Kinase C-η Deficiency Does Not Impair Antiviral Immunity and CD8

Liu, Hsin-Yu / Pedros, Christophe / Kong, Kok-Fai / Canonigo-Balancio, Ann J / Altman, Amnon

Journal of immunology (Baltimore, Md. : 1950)

2020 Volume 204, Issue 9, Page(s) 2439–2446

Abstract: We reported that protein kinase C-η (PKCη) forms a novel (to our knowledge) signaling complex with the checkpoint inhibitory protein CTLA-4 in regulatory T cells (Tregs). This complex is required for the contact-dependent suppressive activity of Tregs, ... ...

Abstract	We reported that protein kinase C-η (PKCη) forms a novel (to our knowledge) signaling complex with the checkpoint inhibitory protein CTLA-4 in regulatory T cells (Tregs). This complex is required for the contact-dependent suppressive activity of Tregs, including suppression of antitumor immunity. However, the importance of PKCη in protective immunity mediated by T effector cells remains unclear. We used mice with germline or conditional Treg-specific deletion of
MeSH term(s)	Animals ; Humans ; Mice ; CD8-Positive T-Lymphocytes/drug effects ; CD8-Positive T-Lymphocytes/immunology ; Cell Line ; Cell Proliferation/drug effects ; CTLA-4 Antigen/immunology ; Granzymes/immunology ; HEK293 Cells ; Immunity, Cellular/drug effects ; Immunity, Cellular/immunology ; Interferon-gamma/immunology ; Lymphocyte Activation/drug effects ; Lymphocyte Activation/immunology ; Lymphocytic choriomeningitis virus/immunology ; Mice, Knockout ; Protein Kinase C/deficiency ; Protein Kinase C/immunology ; Protein Kinase Inhibitors/immunology ; Protein Kinase Inhibitors/pharmacology ; T-Lymphocytes, Regulatory/drug effects ; T-Lymphocytes, Regulatory/immunology ; Virus Diseases/immunology
Chemical Substances	CTLA-4 Antigen ; Granzymes (EC 3.4.21.-) ; Interferon-gamma (82115-62-6) ; Protein Kinase C (EC 2.7.11.13) ; protein kinase C eta (EC 2.7.1.-) ; Protein Kinase Inhibitors
Language	English
Publishing date	2020-03-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1900963
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Article ; Online: Leveraging the Treg-intrinsic CTLA4-PKCη signaling pathway for cancer immunotherapy.

Liu, Hsin-Yu / Pedros, Christophe / Kong, Kok-Fai / Canonigo-Balancio, Ann J / Xue, Wen / Altman, Amnon

Journal for immunotherapy of cancer

2021 Volume 9, Issue 9

Abstract: Background: Our previous studies revealed a critical role of a novel CTLA4-protein kinase C-eta (PKCη) signaling axis in mediating the suppressive activity of regulatory T cells (Tregs) in antitumor immunity. These studies have employed adoptive ... ...

Abstract	Background: Our previous studies revealed a critical role of a novel CTLA4-protein kinase C-eta (PKCη) signaling axis in mediating the suppressive activity of regulatory T cells (Tregs) in antitumor immunity. These studies have employed adoptive transfer of germline PKCη-deficient ( Methods: We have analyzed the role of PKCη in antitumor immunity and the tumor microenvironment (TME) in intact tumor-bearing mice with Treg-specific or CD8 Results: Using two models of mouse transplantable cancer and a genetically engineered autochthonous hepatocellular carcinoma (HCC) model, we found, first, that mice with Treg-specific Conclusion: These findings demonstrate the potential utility of PKCη inhibition as a viable clinical approach to treat patients with cancer, especially when combined with adjuvant therapies.
MeSH term(s)	Animals ; CTLA-4 Antigen/metabolism ; Humans ; Immunotherapy/methods ; Mice ; Neoplasms/drug therapy ; Neoplasms/genetics ; T-Lymphocytes, Regulatory
Chemical Substances	CTLA-4 Antigen ; CTLA4 protein, human
Language	English
Publishing date	2021-09-29
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2021-002792
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Article: A Novel Affinity Engineered Anti-CD47 Antibody With Improved Therapeutic Index That Preserves Erythrocytes and Normal Immune Cells.

Thaker, Youg R / Rivera, Ianne / Pedros, Christophe / Singh, Alok R / Rivero-Nava, Laura / Zhou, Heyue / Swanson, Barbara A / Kerwin, Lisa / Zhang, Yanliang / Gray, J Dixon / Kaufmann, Gunnar F / Ji, Henry / Allen, Robert D / Bresson, Damien

Frontiers in oncology

2022 Volume 12, Page(s) 884196

Abstract: Therapeutic blockade of the CD47/SIRPα axis by small molecules or monoclonal antibodies (mAbs) is a proven strategy to enhance macrophages-mediated anti-tumor activity. However, this strategy has been hampered by elevated on-target toxicities and rapid ... ...

Abstract	Therapeutic blockade of the CD47/SIRPα axis by small molecules or monoclonal antibodies (mAbs) is a proven strategy to enhance macrophages-mediated anti-tumor activity. However, this strategy has been hampered by elevated on-target toxicities and rapid clearance due to the extensive CD47 expression on normal cells ("antigen sink") such as red blood cells (RBCs). To address these hurdles, we report on the development of STI-6643, an affinity-engineered fully human anti-CD47 IgG
Language	English
Publishing date	2022-05-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.884196
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Article ; Online: Disrupted regulatory T cell homeostasis in inflammatory bowel diseases.

Pedros, Christophe / Duguet, Fanny / Saoudi, Abdelhadi / Chabod, Marianne

World journal of gastroenterology

2016 Volume 22, Issue 3, Page(s) 974–995

Abstract: In the gut, where billions of non-self-antigens from the food and the microbiota are present, the immune response must be tightly regulated to ensure both host protection against pathogenic microorganisms and the absence of immune-related pathologies. It ...

Abstract	In the gut, where billions of non-self-antigens from the food and the microbiota are present, the immune response must be tightly regulated to ensure both host protection against pathogenic microorganisms and the absence of immune-related pathologies. It has been well documented that regulatory T cells (Tregs) play a pivotal role in this context. Indeed, Tregs are able to prevent excessive inflammation, which can lead to the rupture of intestinal homeostasis observed in inflammatory bowel diseases (IBDs). Both the worldwide incidence and prevalence of such diseases have increased throughout the latter part of the 20(th) century. Therefore, it is crucial to understand how Tregs suppress the colitogenic immune cells to establish new treatments for patients suffering from IBDs. In this review, we will first summarize the results obtained in animal model studies that highlight the importance of Tregs in maintaining intestinal homeostasis and describe the specific suppressive mechanisms involved. Next, our current knowledge about Tregs contribution to human IBDs will be reviewed, as well as the current therapeutic perspective on using Tregs for clinical IBD treatment and the challenges that remain to be resolved to ensure both the safety and effectiveness of these therapies in targeting this critical immune-regulatory cell population.
MeSH term(s)	Animals ; Gastrointestinal Agents/therapeutic use ; Gastrointestinal Microbiome ; Homeostasis ; Host-Pathogen Interactions ; Humans ; Immunosuppressive Agents/therapeutic use ; Immunotherapy/methods ; Inflammation Mediators/immunology ; Inflammation Mediators/metabolism ; Inflammatory Bowel Diseases/immunology ; Inflammatory Bowel Diseases/metabolism ; Inflammatory Bowel Diseases/microbiology ; Inflammatory Bowel Diseases/therapy ; Intestines/drug effects ; Intestines/immunology ; Intestines/metabolism ; Intestines/microbiology ; Phenotype ; T-Lymphocytes, Regulatory/drug effects ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; T-Lymphocytes, Regulatory/microbiology
Chemical Substances	Gastrointestinal Agents ; Immunosuppressive Agents ; Inflammation Mediators
Language	English
Publishing date	2016-01-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2185929-2
ISSN	2219-2840 ; 1007-9327
ISSN (online)	2219-2840
ISSN	1007-9327
DOI	10.3748/wjg.v22.i3.974
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Article ; Online: Requirement of Treg-intrinsic CTLA4/PKCη signaling pathway for suppressing tumor immunity.

Pedros, Christophe / Canonigo-Balancio, Ann J / Kong, Kok-Fai / Altman, Amnon

JCI insight

2017 Volume 2, Issue 23

Abstract: The ability of Tregs to control the development of immune responses is essential for maintaining immune system homeostasis. However, Tregs also inhibit the development of efficient antitumor responses. Here, we explored the characteristics and ... ...

Abstract	The ability of Tregs to control the development of immune responses is essential for maintaining immune system homeostasis. However, Tregs also inhibit the development of efficient antitumor responses. Here, we explored the characteristics and mechanistic basis of the Treg-intrinsic CTLA4/PKCη signaling pathway that we recently found to be required for contact-dependent Treg-mediated suppression. We show that PKCη is required for the Treg-mediated suppression of tumor immunity in vivo. The presence of PKCη-deficient (Prkch-/-) Tregs in the tumor microenvironment was associated with a significantly increased expression of the costimulatory molecule CD86 on intratumoral CD103+ DCs, enhanced priming of antigen-specific CD8+ T cells, and greater levels of effector cytokines produced by these cells. Similar to mouse Tregs, the GIT/PAK/PIX complex also operated downstream of CTLA4 and PKCη in human Tregs, and GIT2 knockdown in Tregs promoted antitumor immunity. Collectively, our data suggest that targeting the CTLA4/PKCη/GIT/PAK/PIX signaling pathway in Tregs could represent a novel immunotherapeutic strategy to alleviate the negative impact of Tregs on antitumor immune responses.
MeSH term(s)	Animals ; B7-2 Antigen/metabolism ; CTLA-4 Antigen/immunology ; Female ; Heterografts ; Humans ; Immune Tolerance ; Lymphocytes, Tumor-Infiltrating/immunology ; Male ; Melanoma, Experimental/immunology ; Mice, Inbred C57BL ; Mice, Transgenic ; Neoplasm Transplantation ; Prostatic Neoplasms/immunology ; Protein Kinase C/immunology ; Signal Transduction/immunology ; T-Lymphocytes, Regulatory/immunology ; Tumor Escape/immunology ; Tumor Microenvironment/immunology
Chemical Substances	B7-2 Antigen ; CTLA-4 Antigen ; CTLA4 protein, human ; Cd86 protein, mouse ; protein kinase C eta (EC 2.7.1.-) ; Protein Kinase C (EC 2.7.11.13)
Language	English
Publishing date	2017-12-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.95692
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Article ; Online: Quality of Life and Caregiver Burden of Alzheimer's Disease Among Community Dwelling Patients in Europe: Variation by Disease Severity and Progression.

Froelich, Lutz / Lladó, Albert / Khandker, Rezaul K / Pedrós, Montse / Black, Christopher M / Sánchez Díaz, Emilio J / Chekani, Farid / Ambegaonkar, Baishali

Journal of Alzheimer's disease reports

2021 Volume 5, Issue 1, Page(s) 791–804

Abstract: Background: Alzheimer's disease (AD) is a significant burden on patients and caregivers. How this burden increases as disease progresses has not been well researched.: Objective: To assess the association of caregiver burden and quality of life with ... ...

Abstract	Background: Alzheimer's disease (AD) is a significant burden on patients and caregivers. How this burden increases as disease progresses has not been well researched. Objective: To assess the association of caregiver burden and quality of life with Alzheimer's disease severity and disease progression in community-dwelling patients in Germany, Spain, and the UK. Methods: This was a prospective observational longitudinal study of mild-to-moderate AD patients (assessed by Mini-Mental State Examination, MMSE), and their caregivers. The humanistic burden was assessed using these instruments: [Rapid Assessment of Physical Activity (RAPA), EuroQoL-5-Dimension Level (EQ-5D-5L)] and caregiver-reported [Dependence Scale (DS), EQ-5D-5L, Zarit Burden Interview (ZBI)]. Caregiver-reported healthcare resource use was assessed using the Resource Use in Dementia (RUD) and ad-hoc questions. Results: Of 616 patients recruited, 338 and 99 were followed-up at 12 and 18 months, respectively. The caregiver-reported EQ-5D-5L scores of patients' health-related quality of life (HRQoL) showed a negative trend over time (baseline: 0.76; 18 months: 0.67) while patient-reported HRQoL remained at 0.85. DS scores tended to worsen. Disease progression was an independent predictor of HRQoL and increased dependence.Mean ZBI score increased over time reflecting an increase in caregiver burden; MMSE being an independent predictor for caregiver burden. Patient resource utilization and caregiver time for caregiving tended to increase over time. Conclusion: We found significant association between disease progression and caregiver and patient burden. Independently, both disease-specific outcomes and disease burden measures increased over time, but as disease progresses, we also found incremental burden associated with it.
Language	English
Publishing date	2021-10-25
Publishing country	Netherlands
Document type	Journal Article
ISSN	2542-4823
ISSN (online)	2542-4823
DOI	10.3233/ADR-210025
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Article ; Online: Erratum: A TRAF-like motif of the inducible costimulator ICOS controls development of germinal center TFH cells via the kinase TBK1.

Pedros, Christophe / Zhang, Yaoyang / Hu, Joyce K / Choi, Youn Soo / Canonigo-Balancio, Ann J / Yates, John R / Altman, Amnon / Crotty, Shane / Kong, Kok-Fai

Nature immunology

2016 Volume 17, Issue 8, Page(s) 1005

Language	English
Publishing date	2016-07-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/ni0816-1005b
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Article ; Online: Single-photon emission from single-electron transport in a SAW-driven lateral light-emitting diode.

Hsiao, Tzu-Kan / Rubino, Antonio / Chung, Yousun / Son, Seok-Kyun / Hou, Hangtian / Pedrós, Jorge / Nasir, Ateeq / Éthier-Majcher, Gabriel / Stanley, Megan J / Phillips, Richard T / Mitchell, Thomas A / Griffiths, Jonathan P / Farrer, Ian / Ritchie, David A / Ford, Christopher J B

Nature communications

2020 Volume 11, Issue 1, Page(s) 917

Abstract: The long-distance quantum transfer between electron-spin qubits in semiconductors is important for realising large-scale quantum computing circuits. Electron-spin to photon-polarisation conversion is a promising technology for achieving free-space or ... ...

Abstract	The long-distance quantum transfer between electron-spin qubits in semiconductors is important for realising large-scale quantum computing circuits. Electron-spin to photon-polarisation conversion is a promising technology for achieving free-space or fibre-coupled quantum transfer. In this work, using only regular lithography techniques on a conventional 15 nm GaAs quantum well, we demonstrate acoustically-driven generation of single photons from single electrons, without the need for a self-assembled quantum dot. In this device, a single electron is carried in a potential minimum of a surface acoustic wave (SAW) and is transported to a region of holes to form an exciton. The exciton then decays and creates a single optical photon within 100 ps. This SAW-driven electroluminescence, without optimisation, yields photon antibunching with g
Language	English
Publishing date	2020-02-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-020-14560-1
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Article ; Online: A TRAF-like motif of the inducible costimulator ICOS controls development of germinal center TFH cells via the kinase TBK1.

Pedros, Christophe / Zhang, Yaoyang / Hu, Joyce K / Choi, Youn Soo / Canonigo-Balancio, Ann J / Yates, John R / Altman, Amnon / Crotty, Shane / Kong, Kok-Fai

Nature immunology

2016 Volume 17, Issue 7, Page(s) 825–833

Abstract: Signaling via the inducible costimulator ICOS fuels the stepwise development of follicular helper T cells (TFH cells). However, a signaling pathway unique to ICOS has not been identified. We found here that the kinase TBK1 associated with ICOS via a ... ...

Abstract	Signaling via the inducible costimulator ICOS fuels the stepwise development of follicular helper T cells (TFH cells). However, a signaling pathway unique to ICOS has not been identified. We found here that the kinase TBK1 associated with ICOS via a conserved motif, IProx, that shares homology with the tumor-necrosis-factor receptor (TNFR)-associated factors TRAF2 and TRAF3. Disruption of this motif abolished the association of TBK1 with ICOS, TRAF2 and TRAF3, which identified a TBK1-binding consensus. Alteration of this motif in ICOS or depletion of TBK1 in T cells severely impaired the differentiation of germinal center (GC) TFH cells and the development of GCs, interfered with B cell differentiation and disrupted the development of antibody responses, but the IProx motif and TBK1 were dispensable for the early differentiation of TFH cells. These results reveal a previously unknown ICOS-TBK1 signaling pathway that specifies the commitment of GC TFH cells.
MeSH term(s)	Animals ; Antibody Formation/genetics ; B-Lymphocytes/physiology ; CD4-Positive T-Lymphocytes/physiology ; Cell Differentiation/genetics ; Cells, Cultured ; Germinal Center/immunology ; Inducible T-Cell Co-Stimulator Protein/genetics ; Inducible T-Cell Co-Stimulator Protein/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Protein Binding ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/metabolism ; Signal Transduction ; TNF Receptor-Associated Factor 2/genetics ; TNF Receptor-Associated Factor 3/genetics
Chemical Substances	Icos protein, mouse ; Inducible T-Cell Co-Stimulator Protein ; TNF Receptor-Associated Factor 2 ; TNF Receptor-Associated Factor 3 ; Tbk1 protein, mouse (EC 2.7.1.-) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2016-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/ni.3463
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