The differentiation and plasticity of Tc17 cells are regulated by CTLA-4-mediated effects on STATs

Arra, Aditya; Lingel, Holger; Kuropka, Benno; Pick, Jonas; Schnoeder, Tina M.; Fischer, Thomas; Freund, Christian; Pierau, Mandy; Brunner‐Weinzierl, Monika C.

doi:10.1080/2162402x.2016.1273300

Cited by 24 publications

(20 citation statements)

References 65 publications

(99 reference statements)

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“…In addition to RORγt, RORα and IRF4, cytotoxic T lymphocyte antigen (CTLA)-4 was also shown to have a marked effect on Tc17 development by controlling STAT3 activity and thereby downstream genes such as IL-17, IL-21 and RORγt. Tc17 cells lacking CTLA-4 display diminished type 17 signature molecules and a shift towards a CTL phenotype associated with enhanced tumor control, thus identifying CTLA-4 as a molecular switch between Tc17 and CTL fate [35] (Fig. 2).…”

Section: Tc17 Cell Promoting Factorsmentioning

confidence: 99%

Tc17 biology and function: Novel concepts

2020

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Research over the past years has provided increasing understanding about IL‐17‐producing CD8+ T cells termed Tc17 or IL‐17+CD8+ T cells, their distribution and role in a range of diverse immune processes. These comprise resistance to pathogens and tissue homeostasis, but also contribution to autoimmunity and cancer, as well as involvement in gut inflammation, lung diseases and graft‐versus‐host‐disease. Tc17 cells are regulated by unique differentiation mechanisms distinguishing them from other IL‐17‐producing T cells, including Th17, mucosal‐associated invariant T cells, and γδ17 T cells, thus ensuring their specific function in immune responses. Here, we review recent advances in understanding Tc17 cell differentiation and function, and highlight experimental evidence from human studies on patients suffering from organ‐specific autoimmunity including psoriasis, spondyloarthritis and MS as well as from ulcerative colitis and gastrointestinal tract‐associated cancers. We also discuss mouse models analyzing Tc17 characteristics and indicate mechanisms of cross‐talk between Tc17 cells and immune or nonimmune cells, enabling their effector function in both protective as well as pathologic immune responses.

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Section: Tc17 Cell Promoting Factorsmentioning

confidence: 99%

Tc17 biology and function: Novel concepts

2020

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“…TIM-3 + endothelial cells modulate T-cell response to lymphoma surrogate antigens by suppressing activation of CD4 + T lymphocytes through the activation of the IL-6-STAT3 pathway, inhibiting Th1 polarization and providing protective immunity [192]. Finally, CTLA-4 critically shapes the characteristics of IL-17 producing CD8 + cells (Tc17 a pro-tumoral population) in a STAT3 activation-dependent manner and inhibition of CTLA-4-induced STAT3 activity reverses Tc17 signature to Tc1-like cells with enhanced cytotoxic potential [193].…”

Section: Stat3 and Check Points Inhibitorsmentioning

confidence: 99%

STAT3, a Master Regulator of Anti-Tumor Immune Response

Rébé

Ghiringhelli

2019

Cancers

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Immune cells in the tumor microenvironment regulate cancer growth. Thus cancer progression is dependent on the activation or repression of transcription programs involved in the proliferation/activation of lymphoid and myeloid cells. One of the main transcription factors involved in many of these pathways is the signal transducer and activator of transcription 3 (STAT3). In this review we will focus on the role of STAT3 and its regulation, e.g., by phosphorylation or acetylation in immune cells and how it might impact immune cell function and tumor progression. Moreover, we will review the ability of STAT3 to regulate checkpoint inhibitors.

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“…Anti-CTLA-4 and anti-PD-1 effects on antibodies may also modulate T-cell movement within the tumor mass. (1) ( 5 , 43 ), (2) ( 28 – 30 , 74 ), (3) ( 49 ), (4) ( 35 , 45 ), (5) ( 3 , 4 , 32 ), (6) ( 65 , 69 ), (7) ( 10 , 31 , 32 ), (8) ( 25 , 26 , 37 , 38 ). The scheme was drawn using pictures from Servier Medical Art.…”

Section: Ctla-4 and Pd-1 Blockade In Tumor Modelsmentioning

confidence: 99%

CTLA-4 and PD-1 Control of T-Cell Motility and Migration: Implications for Tumor Immunotherapy

2018

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CTLA-4 is a co-receptor on T-cells that controls peripheral tolerance and the development of autoimmunity. Immune check-point blockade (ICB) uses monoclonal antibodies (MAbs) to block the binding of inhibitory receptors (IRs) to their natural ligands. A humanized antibody to CTLA-4 was first approved clinically followed by the use of antibody blockade against PD-1 and its ligand PD-L1. Effective anti-tumor immunity requires the activation of tumor-specific effector T-cells, the blockade of regulatory cells and the migration of T-cells into the tumor. Here, we review data implicating CTLA-4 and PD-1 in the motility of T-cells with a specific reference to the potential exploitation of these pathways for more effective tumor infiltration and eradication.

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The differentiation and plasticity of Tc17 cells are regulated by CTLA-4-mediated effects on STATs

Cited by 24 publications

References 65 publications

Tc17 biology and function: Novel concepts

Tc17 biology and function: Novel concepts

STAT3, a Master Regulator of Anti-Tumor Immune Response

CTLA-4 and PD-1 Control of T-Cell Motility and Migration: Implications for Tumor Immunotherapy

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