Mottas Inès, Bekdemir Ahmet, Cereghetti Alessandra, Spagnuolo Lorenzo, Yang Yu-Sang Sabrina, Müller Marie, Irvine Darrell J., Stellacci Francesco, Bourquin Carole (2019), Amphiphilic nanoparticle delivery enhances the anticancer efficacy of a TLR7 ligand via local immune activation, in Biomaterials
, 190-191, 111-120.
Lucke Matthias, Mottas Inès, Herbst Tina, Hotz Christian, Römer Lin, Schierling Martina, Herold Heike M., Slotta Ute, Spinetti Thibaud, Scheibel Thomas, Winter Gerhard, Bourquin Carole, Engert Julia (2018), Engineered hybrid spider silk particles as delivery system for peptide vaccines, in Biomaterials
, 172, 105-115.
Oberson Anne, Spagnuolo Lorenzo, Puddinu Viola, Barchet Winfried, Rittner Karola, Bourquin Carole (2018), NAB2 is a novel immune stimulator of MDA-5 that promotes a strong type I interferon response, in Oncotarget
, 9(5), 5641-5651.
Widmer Jérôme, Thauvin Cédric, Mottas Inès, Nguyen Van Nga, Delie Florence, Allémann Eric, Bourquin Carole (2018), Polymer-based nanoparticles loaded with a TLR7 ligand to target the lymph node for immunostimulation, in International Journal of Pharmaceutics
, 535(1-2), 444-451.
Mottas Inès, Milosevic Ana, Petri-Fink Alke, Rothen-Rutishauser Barbara, Bourquin Carole (2017), A rapid screening method to evaluate the impact of nanoparticles on macrophages, in Nanoscale
, 9(7), 2492-2504.
Priebe Magdalena, Widmer Jérôme, Suhartha Löwa Nina, Abram Sarah-Luise, Mottas Inès, Woischnig Anne-Kathrin, Brunetto Priscilla S., Khanna Nina, Bourquin Carole, Fromm Katharina M. (2017), Antimicrobial silver-filled silica nanorattles with low immunotoxicity in dendritic cells, in Nanomedicine: Nanotechnology, Biology and Medicine
, 13(1), 11-22.
Hotz Christian, Treinies Marina, Mottas Ines, Rötzer Laurin C., Oberson Anne, Spagnuolo Lorenzo, Perdicchio Maurizio, Spinetti Thibaud, Herbst Tina, Bourquin Carole (2016), Reprogramming of TLR7 signaling enhances antitumor NK and cytotoxic T cell responses, in OncoImmunology
, 5(11), e1232219-e1232219.
Spinetti Thibaud, Spagnuolo Lorenzo, Mottas Inès, Secondini Chiara, Treinies Marina, Rüegg Curzio, Hotz Christian, Bourquin Carole (2016), TLR7-based cancer immunotherapy decreases intratumoral myeloid-derived suppressor cells and blocks their immunosuppressive function, in OncoImmunology
, 5(11), e1230578-e1230578.
Heidegger Simon, Gößl Dorothée, Schmidt Alexandra, Niedermayer Stefan, Argyo Christian, Endres Stefan, Bein Thomas, Bourquin Carole (2016), Immune response to functionalized mesoporous silica nanoparticles for targeted drug delivery, in Nanoscale
, 8(2), 938-948.
Anz David, Rapp Moritz, Eiber Stephan, Koelzer Viktor H., Thaler Raffael, Haubner Sascha, Knott Max, Nagel Sarah, Golic Michaela, Wiedemann Gabriela M., Bauernfeind Franz, Wurzenberger Cornelia, Hornung Veit, Scholz Christoph, Mayr Doris, Rothenfusser Simon, Endres Stefan, Bourquin Carole (2015), Suppression of Intratumoral CCL22 by Type I Interferon Inhibits Migration of Regulatory T Cells and Blocks Cancer Progression, in Cancer Research
, 75(21), 4483-4493.
Hotz Christian, Roetzer Laurin C., Huber Thomas, Sailer Andreas, Oberson Anne, Treinies Marina, Heidegger Simon, Herbst Tina, Endres Stefan, Bourquin Carole (2015), TLR and RLR Signaling Are Reprogrammed in Opposite Directions after Detection of Viral Infection, in The Journal of Immunology
, 195(9), 4387-4395.
Cancer immunotherapy has reached a breakthrough in 2013 with the advent of drugs based on immune checkpoint blockade. However, even the most effective treatment options in immunotherapy, including the adoptive transfer of tumor-specific T cells into patients, result in an objective clinical response in only a minority of patients. One reason may be that many tumors lack the ability to recruit cytotoxic T cells, which can render them resistant to current immunotherapy approaches. Strategies that reinforce the migration of T cells into tumors are therefore urgently needed to complement existing treatments that foster the antitumor effector function of T cells. In a model of gastric cancer, we have previously demonstrated that T cells do not infiltrate the tumors, even upon adoptive transfer of tumor-specific T cells. We have recently developed a treatment protocol with a combination of Rig-I-like receptor (RLR) and Toll-like receptor (TLR) ligands that induces strong innate immune activation and greatly enhances CD8 T-cell recruitment to the gastric tumors. We propose to study the mechanisms that support intratumoral T-cell accumulation in this model. Specifically, we aim to:•Discover new factors and pathways that foster T-cell migration into tumors•Combine RLR/TLR-based therapy with treatments targeting antitumoral T-cell function to further improve the outcome•Use our expertise in nanoparticle-based drug delivery to augment the specificity of RLR/TLR therapyThe output from this project will lead to a better understanding of how cytotoxic T cells infiltrate gastric tumors and how recruitment of these cells can be induced by pharmacologic intervention. This knowledge will be of high relevance for improving the outcome of immunotherapeutic strategies to treat gastric cancer and other gastrointestinal tumors. The insights obtained in this project may direct impact the design of future translational studies in cancer immunotherapy.