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Università della Svizzera italiana

Is there a role for dual PI3K/mTOR inhibitors for patients affected with lymphoma?

Tarantelli, Chiara ; Lupia, Antonio ; Stathis, Anastasios ; Bertoni, Francesco

In: International journal of molecular sciences, 2020, vol. 21, no. 3, p. 21 p

The activation of the PI3K/AKT/mTOR pathway is a main driver of cell growth, proliferation, survival, and chemoresistance of cancer cells, and, for this reason, represents an attractive target for developing targeted anti- cancer drugs. There are plenty of preclinical data sustaining the anti-tumor activity of dual PI3K/mTOR inhibitors as single agents and in combination in lymphomas. Clinical...

Université de Fribourg

Modulation of calretinin expression in human mesothelioma cells reveals the implication of the fak and wnt signaling pathways in conferring chemoresistance towards cisplatin

Wörthmüller, Janine ; Salicio, Valérie ; Oberson, Anne ; Blum, Walter ; Schwaller, Beat

In: International Journal of Molecular Sciences, 2019, vol. 20, no. 21, p. 5391

Malignant mesothelioma (MM) is an aggressive asbestos-linked neoplasm, characterized by dysregulation of signaling pathways. Due to intrinsic or acquired chemoresistance, MM treatment options remain limited. Calretinin is a Ca2+-binding protein expressed during MM tumorigenesis that activates the FAK signaling pathway, promoting invasion and epithelial-to-mesenchymal transition. Constitutive...

Università della Svizzera italiana

DNA (hydroxy)methylation in T helper lymphocytes

Monticelli, Silvia

In: Trends in biochemical sciences, 2019, vol. 44, no. 7, p. 589-598

Upon recognition of an antigen, the differentiation of antigen-inexperienced naïve T lymphocytes into subsets able to effectively coordinate host defense is controlled by a network of transcription factors and regulatory molecules. In the cell nucleus, these factors act in the context of epigenetic modifications that influence DNA accessibility and ultimately gene expression. This review...

Université de Fribourg

Initial viral inoculum determines kinapse-and synapse-like t cell motility in reactive lymph nodes

Sivapatham, Sujana ; Ficht, Xenia ; Albuquerque, Juliana Barreto de ; Page, Nicolas ; Merkler, Doron ; Stein, Jens V.

In: Frontiers in Immunology, 2019, vol. 10, p. -

T cell activation in lymphoid tissue occurs through interactions with cognate peptide- major histocompatibility complex (pMHC)-presenting dendritic cells (DCs). Intravital imaging studies using ex vivo peptide-pulsed DCs have uncovered that cognate pMHC levels imprint a wide range of dynamic contacts between these two cell types. T cell—DC interactions vary between transient,...

Université de Fribourg

Are integrins still practicable targets for anti-cancer therapy?

Alday-Parejo, Begoña ; Stupp, Roger ; Rüegg, Curzio

In: Cancers, 2019, vol. 11, no. 7, p. 978

Correlative clinical evidence and experimental observations indicate that integrin adhesion receptors, in particular those of the αV family, are relevant to cancer cell features, including proliferation, survival, migration, invasion, and metastasis. In addition, integrins promote events in the tumor microenvironment that are critical for tumor progression and metastasis, including tumor...

Università della Svizzera italiana

Epicutaneous allergen application preferentially boosts specific T cell responses in sensitized patients

Campana, Raffaela ; Moritz, Katharina ; Neubauer, Angela ; Huber, Hans ; Henning, Rainer ; Brodie, Tess M. ; Kaider, Alexandra ; Sallusto, Federica ; Wöhrl, Stefan ; Valenta, Rudolf

In: Scientific reports, 2017, vol. 7, p. 11657

The effects of epicutaneous allergen administration on systemic immune responses in allergic and non-allergic individuals has not been investigated with defined allergen molecules. We studied the effects of epicutaneous administration of rBet v 1 and rBet v 1 fragments on systemic immune responses in allergic and non-allergic subjects. We conducted a clinical trial in which rBet v 1 and two...

Université de Fribourg

Polymer-coated gold nanospheres do not impair the innate immune function of human b lymphocytes in vitro

Hočevar, Sandra ; Milošević, Ana ; Rodriguez-Lorenzo, Laura ; Ackermann-Hirschi, Liliane ; Mottas, Ines ; Petri-Fink, 6 Alke ; Rothen-Rutishauser, Barbara ; Bourquin, Carole ; Clift, Martin James David

In: ACS Nano, 2019, vol. 13, no. 6, p. 6790–6800

Gold nanoparticles (GNPs) are intended for use within a variety of biomedical applications due to their physicochemical properties. Although, in general, biocompatibility of GNPs with immune cells such as macrophages and dendritic cells is well established, the impact of GNPs on B lymphocyte immune function remains to be determined. Since B lymphocytes play an important role in health and...

Università della Svizzera italiana

TET2 regulates mast cell differentiation and proliferation through catalytic and non-catalytic activities

Montagner, Sara ; Leoni, Cristina ; Emming, Stefan ; Della Chiara, Giulia ; Balestrieri, Chiara ; Barozzi, Iros ; Piccolo, Viviana ; Togher, Susan ; Ko, Myunggon ; Rao, Anjana ; Natoli, Gioacchino ; Monticelli, Silvia

In: Cell reports, 2016, vol. 15, no. 7, p. 1566-1579

Dioxygenases of the TET family impact genome functions by converting 5-methylcytosine (5mC) in DNA to 5-hydroxymethylcytosine (5hmC). Here, we identified TET2 as a crucial regulator of mast cell differentiation and proliferation. In the absence of TET2, mast cells showed disrupted gene expression and altered genome-wide 5hmC deposition, especially at enhancers and in the proximity of...

Università della Svizzera italiana

Memory T cells in latent mycobacterium tuberculosis infection are directed against three antigenic islands and largely contained in a CXCR3+CCR6+ Th1 subset

Lindestam Arlehamn, Cecilia S. ; Gerasimova, Anna ; Mele, Federico ; Henderson, Ryan ; Swann, Justine ; Greenbaum, Jason A. ; Kim, Yohan ; Sidney, John ; James, Eddie A. ; Taplitz, Randy ; McKinney, Denise M. ; Kwok, William W. ; Grey, Howard ; Sallusto, Federica ; Peters, Bjoern ; Sette, Alessandro

In: Plos pathogens, 2013, vol. 9, no. 1, p. e1003130

An understanding of the immunological footprint of Mycobacterium tuberculosis (MTB) CD4 T cell recognition is still incomplete. Here we report that human Th1 cells specific for MTB are largely contained in a CXCR3+CCR6+ memory subset and highly focused on three broadly immunodominant antigenic islands, all related to bacterial secretion systems. Our results refute the notion that secreted...

Università della Svizzera italiana

CCR2 acts as scavenger for CCL2 during monocyte chemotaxis

Volpe, Silvia ; Cameroni, Elisabetta ; Moepps, Barbara ; Thelen, Sylvia ; Apuzzo, Tiziana ; Thelen, Marcus

In: Plos one, 2012, vol. 7, no. 5, p. e37208

Background: Leukocyte migration is essential for effective host defense against invading pathogens and during immune homeostasis. A hallmark of the regulation of this process is the presentation of chemokines in gradients stimulating leukocyte chemotaxis via cognate chemokine receptors. For efficient migration, receptor responsiveness must be maintained whilst the cells crawl on cell surfaces...