The transcription factor IRF1 dictates the IL-21-dependent anticancer functions of TH9 cells

Végran, Frédérique; Berger, H.; Boidot, Romain; Mignot, Grégoire; Bruchard, Mélanie; Dosset, Magalie; Chalmin, Fanny; Rébé, Cédric; Dérangère, Valentin; Ryffel, Bernhard; Kato, Masashi; Prévost-Blondel, Armelle; Ghiringhelli, François; Apétoh, Lionel

doi:10.1038/ni.2925

Cited by 190 publications

(201 citation statements)

References 49 publications

Supporting

Mentioning

191

Contrasting

Unclassified

Order By: Relevance

“…Moreover, Th9 cells release IL-21, which promotes the production of IFNg and tumor elimination by CD8 C T cells and NK cells. 113 The relevance of Th9 cells in thyroid oncogenesis remains to be elucidated. Fig.…”

Section: Natural Killer T Cells (Nkt) Gd T Cells and Innate Lymphoidmentioning

confidence: 99%

The immune network in thyroid cancer

2016

View full text Add to dashboard Cite

The immune system plays critical roles in tumor prevention, but also in its initiation and progression. Tumors are subjected to immunosurveillance, but cancer cells generate an immunosuppressive microenvironment that favors their escape from immune-mediated elimination. During chronic inflammation, immune cells can contribute to the formation and progression of tumors by producing mitogenic, prosurvival, proangiogenic and lymphangiogenic factors. Thyroid cancer is the most frequent type of endocrine neoplasia and is the most rapidly increasing cancer in the US. In this review, we discuss recent findings on how different immune cells and mediators can contribute to thyroid cancer development and progression.

show abstract

Section: Natural Killer T Cells (Nkt) Gd T Cells and Innate Lymphoidmentioning

confidence: 99%

The immune network in thyroid cancer

2016

View full text Add to dashboard Cite

show abstract

“…IRF1 is a Th1 transcription factor that is expressed in Th9 cells upon stimulation with IL1b. This factor binds directly on il9 and il21 promoters, and is essential to boost production of both cytokines (15). This factor is a powerful enhancer of the Th9 program.…”

Section: Transcriptional Program Of Th9 Cellsmentioning

confidence: 99%

“…Mouse and human Th9 cells secrete IL9 and IL21 and were initially proposed to contribute to the development of autoimmune and allergic diseases (11,12). We and others, however, recently found that Th9 cells also featured potent anticancer properties (13)(14)(15). In this review, we discuss the potential of using Th9 cells for anticancer immunotherapy.…”

mentioning

confidence: 97%

Th9 Cells: A Novel CD4 T-cell Subset in the Immune War against Cancer

2015

Self Cite

View full text Add to dashboard Cite

CD4 T cells are key components of the immune system that shape the anticancer immune response in animal models and in humans. The biology of CD4 T cells is complex because na€ ve T cells can differentiate into various subpopulations with various functions. Recently, a new population called Th9 cells was described. These cells are characterized by their ability to produce IL9 and IL21. They were first described in the context of parasite infections and allergic processes. However, some reports described their presence in the tumor bed in mice and humans. Their high secretion of IL9 and IL21 in the tumor bed contributes to their anticancer functions. Indeed, these cytokines trigger the activation of dendritic cells, mast cells, natural killer cells, and CD8 T cells to mount an antitumor immune response, thus explaining the remarkable ability of Th9 cells to control tumor growth. This review summarizes the latest advances in the Th9 field in cancer and focuses on their potential role as new tool for cell therapy. Cancer Res; 75(3); 475-9. Ó2014 AACR. The Role of CD4 T-cell Polarization in CancerSince the seminal observations of Dunn and colleagues (1) on cancer immunosurveillance, the role of the adaptive immune system in the development of cancer or tumor growth is clearly established. CD4 helper T cells are key elements of the adaptive immune response, and are known to differentiate from a na€ ve population into helper memory populations after stimulation by T-cell receptor (TCR) triggering by the cognate antigen and a particular cocktail of cytokines. The original classification of CD4 T lymphocytes by Mosmann and Colleagues (2) described two populations of effector CD4 T cells called Th1 and Th2 subsets. Th1 are IFNg-producing cells and were known as the classical antitumor cells because of the capacity of IFNg to activate the killer functions of macrophages, natural killer (NK) cells, and CD8 CTLs. Th2 cells are characterized by their production of IL4, and play a central role in the development of asthma and atopic dermatitis. The role of Th2 cells in cancer is mainly deleterious as IL4 directly favors tumor growth. In addition, Th2 cells could induce M2 polarization of tumor-infiltrating macrophages, which drive tumor immune tolerance and neoangiogenesis (3). CD4 T cells are now known to differentiate into additional new effector T-cell subsets like Th17 cells and follicular helper T cells as well as immunosuppressive cells like Foxp3 regulatory T cells. Foxp3 regulatory T cells are well-known immunosuppressive cells. These cells inhibit the anticancer immune response and induce immunosuppression in many cancer types (4). In contrast, the infiltration of tumors by follicular helper T cells seems to be associated with a coordinated antitumoral immune response and a better clinical outcome (5). The role of Th17 cells in cancer remains a matter of debate. IL17 could promote neoangiogenesis and the expression of prosurvival genes in cancer cells (6). In addition, ectonucleotidase-expressing Th17 cells co...

show abstract

“…Ces cellules produisent également de l'IL-3 à des niveaux qui sont équivalents à ceux de l'IL-9 [15]. Jäger et al [16] Lorsque la polarisation par le TGF-b et l'IL-4 est associée à une exposition à une cytokine inflammatoire, l'IL-1b, une forte augmentation de la production d'IL-9 et d'IL-21 par les Th9 est observée [17]. Bien que produisant de l'IL-10, une cytokine anti-inflammatoire, les Th9 semblent dépourvus d'activité immunosuppressive [11], une absence de fonction suppressive qui n'est actuellement pas clairement expliquée.…”

Section: Les Cytokines Exprimées Par Les Lymphocytes Th9unclassified

“…La présence d'IL-1b lors de la polarisation, permet d'augmenter significativement l'activité antitumorale des Th9 ainsi différenciés par rapport à celle des Th9 conventionnels. Cette activité antitumorale est totalement neutralisée par l'adjonction d'anticorps bloquant l'IL-21 contrairement à celle des Th9 conventionnels qui dépend, elle, de la présence d'IL-9 [17]. L'IL-21 est une cytokine pléiotropique qui influence de nombreux types cellulaires : les lymphocytes T CD4 et CD8, les cellules Th17 et Treg, les cellules NK et NKT (T natural killer), les lymphocytes B, les cellules dendritiques et les macrophages [42].…”

Section: Maladies Auto-immunesunclassified