Deciphering the Roles of Innate Lymphoid Cells in Cancer

Cancer is a complex disease and the role played by innate lymphoid cells (ILCs) in cancer development has begun to be uncovered over recent years. We aim to provide an exhaustive summary of the knowledge acquired on the role of ILCs in cancer. ILCs are classified into 3 different categories, ILC1s, ILC2s, and ILC3s, each encompassing specific and unique functions. ILC1s exhibit NK cells characteristics and can exert anti-tumor functions, but surprisingly their IFNγ production is not associated with a better immune response. In response to TGF-β or IL-12, ILC1s were shown to exert pro-tumor functions and to favor tumor growth. ILC2s role in cancer immune response is dependent on cytokine context. The production of IL-13 by ILC2s is associated with a negative outcome in cancer. ILC2s can also produce IL-5, leading to eosinophil activation and an increased anti-tumor immune response in lung cancer. ILC3s produce IL-22, which could promote tumor growth. In contrast, ILC3s recognize tumor cells and facilitate leukocyte tumor entry, increasing anti-tumor immunity. In some contexts, ILC3s were found at the edge of tertiary lymphoid structures, associated with a good prognostic. We are at the dawn of our understanding of ILCs role in cancer. This review aims to thoroughly analyze existing data and to provide a comprehensive overview of our present knowledge on the impact of ILCs in cancer

Etude de NLRP3 dans les cellules myéloïdes immunosuppressives et les lymphocytes TCD4 dans un contexte de cancer

The inflammasome NLRP3 (NOD like receptor pyd containing 3) is a multiprotein complex notably responsible for IL-1β (interleukine-1β) production, an inflammatory cytokine. Negative effects have been observed in various diseases including cancer. My thesis focuses on the effects of NLRP3 in cancer.In my first project, I studied the NLRP3 inflammasome activation in MDSC (myeloïd derived suppressor cells) after a chemotherapy treatment. Two chemotherapies, 5-Fluorouracil and Gemcitabine, are selectively able to kill MDSC, an immunosuppressive population growing during cancer evolution. MDSC’s death restores anti-tumor immunity for a while but another immunosuppressive population is established by MDSC produced IL-1β before their disappearance. I discovered that 5-Fluorouracil and Gemcitabine trigger NLRP3 inflammasome activation in MDSC. 5-Fluorouracil and Gemcitabine induce lysosomal permeabilisation, allowing for Cathepsin B release into the cytoplasm where it directly interacts with NLRP3. That interaction activates the inflammasome and induces IL-1β production which is responsible for the development of another immunosuppressive population, called Th17 cells.I then studied the role of NLRP3 during Th2 differentiation. Here, NLRP3 actions are done independently of the other inflammasome forming proteins. After being induced by IL-2 signalization pathway, NLRP3 interacts with IRF4 (interferon regulatory factor 4) and acts as a transcription factor on the IL-4 promoter gene. Lack of NLRP3 leads to a smaller IL-4 production by Th2 cells which are consequently less functionalL’inflammasome NLRP3 est un complexe multiprotéique responsable notamment de la production d’IL-1β, une cytokine inflammatoire. Les effets délétères de l’inflammasome NLRP3 ont été démontrés dans de nombreuses maladies dont le cancer. Ce travail se concentre sur les effets de NLRP3 dans le contexte du cancer.Dans un premier projet, j’ai étudié l’activation de l’inflammasome NLRP3 dans les MSDC après un traitement par chimiothérapie. Deux chimiothérapies, le 5-Fluorouracile et la Gemcitabine, sont capables d’éliminer de façon spécifique les MDSC, population de cellules immunosuppressives dont la taille augmente en cas de cancer. J’ai découvert que le 5-Fluorouracile et la Gemcitabine activaient l’inflammasome NLRP3 dans les MDSC. En effet, le 5-Fluorouracile et la Gemcitabine provoquent la perméabilisation du lysosome des MDSC, permettant la sortie de la cathepsine B, protéine lysosomale, dans le cytoplasme où elle interagit directement avec NLRP3. Cette interaction active l’inflammasome NLRP3 et la production d’IL-1β. Cette IL-1β est responsable du développement d’une nouvelle population immunosuppressive, les Th17.J’ai ensuite étudié le rôle de NLRP3 dans la différenciation des lymphocytes T CD4 Th2. Dans ces cellules, le rôle de NLRP3 s’effectue indépendamment du reste du complexe multiprotéique qui forme l’inflammasome. Après avoir été induit par la cascade de signalisation de l’IL-2, NLRP3 interagit avec IRF4 (interferon regulatory factor) et agit comme un facteur de transcription sur le promoteur du gène de l’IL-4. L’absence de NLRP3 a pour conséquence une production moins importante d’IL-4 par les Th2 qui sont alors moins fonctionnel

Tradução, edição. William Morris e o livro ideal

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Comunicação e Expressão, Programa de Pós-Graduação em Estudos da Tradução, Florianópolis, 2015.Este tese examina a relação entre tradução e edição, dois ofícios mediadores entre um texto e seu leitor cuja ação se confunde e complementa na transmissão das ideias e das obras. Duas linguagens que, a partir de escolhas verbais ou verbo-visuais, dão nova forma a um texto conferindo-lhe novos significados. Duas formas privilegiadas de reescrita que, entre traição e criação, mantêm vivo um texto original ao atualizá-lo em diferentes línguas, tempos e espaços. Num primeiro momento, é observado o modo como se realizam tradução e edição em diferentes períodos da história do livro, e em que medida, ao refletirem valores e ideologias da cultura em que se inscrevem, espelham o modo como se manifesta, nessa cultura, a relação com o Outro, o estrangeiro. Num segundo momento, é enfocada a obra do artista e poeta William Morris (1834-1896). Tradutor, Morris se destacou por introduzir a literatura nórdica na Inglaterra oitocentista. Editor, produziu com arte, em sua Kelmscott Press, livros que marcaram a história do moderno design editorial. Examina-se aqui, mais detidamente, como se integram tradução e edição num projeto seu de quase vida inteira, a translação das sagas islandesas. E como se integra a translação das sagas com a sua longa busca do livro ideal.Abstract : This thesis examines the relationship between translation and publishing, two professions that mediate between texts and their readers in the transmission of ideas and works through activities that are interrelated, interdependent and often indistinguishable. Two languages that give new form to a text, endowing it with new meanings through verbal or verbal-visual choices. Two privileged forms of rewriting that inhabit the space between betrayal and creation, rejuvenating original texts by bringing them up to date in different languages, times and places. The thesis begins by observing the different modes of translation and publishing that have prevailed during different periods in the history of books and discussing the extent to which these different modes, which reflect the values and ideologies of their host cultures, mirror the way that the relationship with the Other, the foreign, is manifest in these cultures. The thesis then narrows its focus to the work of the artist and poet William Morris (1834-1896). As a Translator, Morris? most significant achievement was to introduce Nordic literature to nineteenth-century England. As an Editor, the pioneering combination of art with publication that he carried on at the Kelmscott Press resulted in productions that have shaped modern book design. This analysis examines in detail the way that Morris integrated translation and publishing in his near-lifelong project to translate the Icelandic sagas and the way that he integrated translation of these sagas into his painstaking quest for the ideal book

'POLIPHILUS' X 'POLIPHILE', OU O SONHO FRANCÊS DE ABSORÇÃO DO HUMANISMO ITALIANO

Hypnerotomachia Poliphili, publicado em Veneza, 1499, por Aldo Manúcio, permanece uma obra emblemática na história do livro ocidental. Introduzido na França em 1596, o entusiasmo com que ali foi recebido contribuiu em larga medida para a vasta fortuna literária desta obra de Francesco Colonna. Um paralelo entre a edição aldina original e sua versão francesa permite ilustrar a estreita relação existente entre tradução e edição, essas duas formas de reescrita (Lefevere 2007) indispensáveis na transmissão e circulação dos textos. Permite observar, além disso, como se expressa no Songe de Poliphile, por esses mediadores indissociáveis na translação das obras (Berman, 1995), a absorção do humanismo italiano por parte da França renascentista

Claire Cayron: Profissão: traductrice/Profession : tradutora

Edição: 1.ª Ed. Editoria: Florianópolis: DLLE/UFSC, Escritório do Livro, 2012. Páginas: 78 p. Língua da publicação: Português e francês Tradução: Ana Carolina Correa da Silva, Bianca Melyna Filgueira, Claudia Borges de Faveri, Diego Conte, Dorothée de Bruchard, Ellen Carina Araujo de Carvalho, Iris Marjorie Böing Imhof, Lia Benthien, Marcia Bioni, Nathália Leite Munari, Teresa Cristina Rodrigues dos Santos & Thays Tomazi Língua do original: Francês e português Comentários: Edição bilíngue. Referência ABNT: Bruchard, Dorothée de (Org.). Claire Cayron: Profissão: traductrice/Profession : tradutora. 1.ª Ed. Florianópolis: DLLE/UFSC, Escritório do Livro, 2012. 78 p. [: Francês e português]. Tradução de: Ana Carolina Correa da Silva, Bianca Melyna Filgueira, Claudia Borges de Faveri, Diego Conte, Dorothée de Bruchard, Ellen Carina Araujo de Carvalho, Iris Marjorie Böing Imhof, Lia Benthien, Marcia Bioni, Nathália Leite Munari, Teresa Cristina Rodrigues dos Santos & Thays Tomazi

Regulation of T cell antitumor immune response by tumor induced metabolic stress

Adaptive T cell immune response is essential for tumor growth control. The efficacy of immune checkpoint inhibitors is regulated by intratumoral immune response. The tumor microenvironment has a major role in adaptive immune response tuning. Tumor cells generate a particular metabolic environment in comparison to other tissues. Tumors are characterized by glycolysis, hypoxia, acidosis, amino acid depletion and fatty acid metabolism modification. Such metabolic changes promote tumor growth, impair immune response and lead to resistance to therapies. This review will detail how these modifications strongly affect CD8 and CD4 T cell functions and impact immunotherapy efficacy

Production of Adenosine by Ectonucleotidases: A Key Factor in Tumor Immunoescape

It is now well known that tumor immunosurveillance contributes to the control of cancer growth. Many mechanisms can be used by cancer cells to avoid the antitumor immune response. One such mechanism relies on the capacity of cancer cells or more generally of the tumor microenvironment to generate adenosine, a major molecule involved in antitumor T cell response suppression. Adenosine is generated by the dephosphorylation of extracellular ATP released by dying tumor cells. The conversion of ATP into adenosine is mediated by ectonucleotidase molecules, namely, CD73 and CD39. These molecules are frequently expressed in the tumor bed by a wide range of cells including tumor cells, regulatory T cells, Th17 cells, myeloid cells, and stromal cells. Recent evidence suggests that targeting adenosine by inhibiting ectonucleotidases may restore the resident antitumor immune response or enhance the efficacy of antitumor therapies. This paper will underline the impact of adenosine and ectonucleotidases on the antitumor response

Pathogenic Fungi Regulate Immunity by Inducing Neutrophilic Myeloid-Derived Suppressor Cells

Peer reviewedPublisher PD

Alum Activates the Bovine NLRP3 Inflammasome

peer-reviewedThere has been a move away from vaccines composed of whole or inactivated antigens toward subunit-based vaccines, which although safe, provide less immunological protection. As a result, the use of adjuvants to enhance and direct adaptive immune responses has become the focus of much targeted bovine vaccine research. However, the mechanisms by which adjuvants work to enhance immunological protection in many cases remains unclear, although this knowledge is critical to the rational design of effective next generation vaccines. This study aimed to investigate the mechanisms by which alum, a commonly used adjuvant in bovine vaccines, enhances IL-1β secretion in bovine peripheral blood mononuclear cells (PBMCs). Unlike the case with human PBMCs, alum promoted IL-1β secretion in a subset of bovine PBMCs without priming with a toll-like receptor agonist. This suggests that PBMCs from some cattle are primed to produce this potent inflammatory cytokine and western blotting confirmed the presence of preexisting pro-IL-1β in PBMCs from a subset of 8-month-old cattle. To address the mechanism underlying alum-induced IL-1β secretion, specific inhibitors identified that alum mediates lysosomal disruption which subsequently activates the assembly of an NLRP3, ASC, caspase-1, and potentially caspase-8 containing complex. These components form an inflammasome, which mediates alum-induced IL-1β secretion in bovine PBMCs. Given the demonstrated role of the NLRP3 inflammasome in regulating adaptive immunity in murine systems, these results will inform further targeted research into the potential of inflammasome activation for rational vaccine design in cattle

Immune-mediated mechanisms influencing the efficacy of anticancer therapies

Conventional anticancer therapies, such as chemotherapy, radiotherapy, and targeted therapy, are designed to kill cancer cells. However, the efficacy of anticancer therapies is not only determined by their direct effects on cancer cells but also by off-target effects within the host immune system. Cytotoxic treatment regimens elicit several changes in immune-related parameters including the composition, phenotype, and function of immune cells. Here we discuss the impact of innate and adaptive immune cells on the success of anticancer therapy. In this context we examine the opportunities to exploit host immune responses to boost tumor clearing, and highlight the challenges facing the treatment of advanced metastatic disease