Publications by George Coukos | EPFL Graph Search

Machine learning predictions of MHC-II specificities reveal alternative binding mode of class II epitopes

Julien Racle, David Gfeller, Philippe Guillaume Coune, Florence Pojer, Marta Andreia Da Silva Perez, George Coukos, Kelvin Ka Ching Lau, Amédé Noredine Larabi, Alexandre Harari

CD4+T cells orchestrate the adaptive immune response against pathogens and cancer by recognizing epitopes presented on class II major histocompatibility complex (MHC-II) molecules. The high polymorphism of MHC-II genes represents an important hurdle toward ...

CELL PRESS2023

p High-Throughput Single-Cell TCR-pMHC Dissociation Rate Measurements Performed by an Autonomous Microfluidic Cellular Processing Unit

Sebastian Maerkl, Fabien Louis Claude Robert Jammes, George Coukos

We developed an integrated microfluidic cellular processing unit (mCPU) capable of autonomously isolating single cells and performing measurements and on-the-fly analysis of cell- surface dissociation rates, followed by recovery of selected cells. We perfo ...

AMER CHEMICAL SOC2022

Cell-autonomous inflammation of BRCA1-deficient ovarian cancers drives both tumor-intrinsic immunoreactivity and immune resistance via STING

Christian Iseli, Julien Dorier, Mauro Delorenzi, Alizée Jéléna Grimm, Marco Mina, George Coukos, Alexandre Harari, Giovanni Ciriello

In this study, we investigate mechanisms leading to inflammation and immunoreactivity in ovarian tumors with homologous recombination deficiency (HRD). BRCA1 loss is found to lead to transcriptional reprogramming in tumor cells and cell-intrinsic inflammat ...

2021

Azole-Based Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitors

Pierre Vogel, Olivier Michielin, Florence Pojer, Somi Reddy Majjigapu, George Coukos

The heme enzyme indoleamine 2,3-dioxygenase 1 (IDO1) plays an essential role in immunity, neuronal function, and aging through catalysis of the rate-limiting step in the kynurenine pathway of tryptophan metabolism. Many IDO1 inhibitors with different chemo ...

AMER CHEMICAL SOC2021

Microfluidic Device for Droplet Pairing by Combining Droplet Railing and Floating Trap Arrays

Philippe Renaud, Margaux Catherine Marie Duchamp, George Coukos, Alexandre Harari, Marion Arnaud

Droplet microfluidics are characterized by the generation and manipulation of discrete volumes of solutions, generated with the use of immiscible phases. Those droplets can then be controlled, transported, analyzed or their content modified. In this wide d ...

MDPI2021

Personalized cancer vaccine strategy elicits polyfunctional T cells and demonstrates clinical benefits in ovarian cancer

Stéphanie Tissot, Johanna Pauline Chiffelle, George Coukos, Alexandre Harari, Florian Huber

T cells are important for controlling ovarian cancer (OC). We previously demonstrated that combinatorial use of a personalized whole-tumor lysate-pulsed dendritic cell vaccine (OCDC), bevacizumab (Bev), and cyclophosphamide (Cy) elicited neoantigen-specifi ...

2021

Tumor-specific cytolytic CD4 T cells mediate immunity against human cancer

David Gfeller, Georg Alexander Rockinger, Pedro Romero, Amélie Cachot, Hatice Altug, Margaux Saillard, Xiaokang Li, George Coukos, Yen-Cheng Liu, Alexandre Harari, Alexander Mathis

CD4 T cells have been implicated in cancer immunity for their helper functions. Moreover, their direct cytotoxic potential has been shown in some patients with cancer. Here, by mining single-cell RNA-seq datasets, we identified CD4 T cell clusters displayi ...

2021

Unsupervised Analysis of Flow Cytometry Data in a Clinical Setting Captures Cell Diversity and Allows Population Discovery

Nicolas Jean Philippe Guex, Fabrizio Benedetti, George Coukos, Ioannis Xenarios, Alexandre Harari

2021

Neutrophils suppress tumor-infiltrating T cells in colon cancer via matrix metalloproteinase-mediated activation of TGF beta

Marc-Olivier Sauvain, Freddy Radtke, Mauro Delorenzi, Nadine Fournier, Markus Germann, George Coukos, Amber Dawn Bowler

High T-cell infiltration in colorectal cancer (CRC) correlates with a favorable disease outcome and immunotherapy response. This, however, is only observed in a small subset of CRC patients. A better understanding of the factors influencing tumor T-cell re ...

2020

A computationally designed chimeric antigen receptor provides a small-molecule safety switch for T-cell therapy

George Coukos, Bruno Emanuel Ferreira De Sousa Correia, Jaume Bonet Martinez, Pablo Gainza Cirauqui, Sabrina Susan Vollers, Sailan Shui

The activity of CAR-T cells is reversibly halted with a small-molecule drug. Approaches to increase the activity of chimeric antigen receptor (CAR)-T cells against solid tumors may also increase the risk of toxicity and other side effects. To improve the s ...

2020

Cathepsin S Regulates Antigen Processing and T Cell Activity in Non-Hodgkin Lymphoma

Julien Racle, Jessica Sordet, Marco Mina, George Coukos, Bruno Emanuel Ferreira De Sousa Correia, Elisa Oricchio, Natalya Katanayeva, Elena Battistello, Stephanie Jocelyne Sungalee, Elie Charles Eugène Dheilly, Sarah Wehrle, Giovanni Ciriello

Genomic alterations in cancer cells can influence the immune system to favor tumor growth. In non-Hodgkin lymphoma, physiological interactions between B cells and the germinal center microenvironment are coopted to sustain cancer cell proliferation. We fou ...

2020

Integrated proteogenomic deep sequencing and analytics accurately identify non-canonical peptides in tumor immunopeptidomes

Didier Trono, Marion Leleu, Evaristo Jose Planet Letschert, George Coukos, Ioannis Xenarios, Laia Simo Riudalbas, Delphine Yvette L Grun, Alexandre Harari, Markus Müller, Lin Zhang, Marion Arnaud, Florian Huber

Efforts to precisely identify tumor human leukocyte antigen (HLA) bound peptides capable of mediating T cell-based tumor rejection still face important challenges. Recent studies suggest that non-canonical tumor-specific HLA peptides derived from annotated ...

Nature Research2020

Disturbed mitochondrial dynamics in CD8(+)TILs reinforce T cell exhaustion

Nicola Vannini, Marcela Rincón-Restrepo, Fabien Franco, George Coukos, Li Tang, Min Gao

Ho and colleagues report that mitochondrial dysfunction and impaired mitophagy triggered by the tumor microenvironment lead to subsequent epigenetic changes and cause permanent T cell exhaustion and dysfunction. The metabolic challenges present in tumors a ...

2020

High-throughput automated organoid culture via stem-cell aggregation in microcavity arrays

Gerardo Turcatti, Matthias Lütolf, Nathalie Brandenberg, Fabien Kuttler, Krisztian Homicsko, Nikolche Gjorevski, George Coukos, Camilla Carla Alma Ceroni

Stem-cell-derived epithelial organoids are routinely used for the biological and biomedical modelling of tissues. However, the complexity, lack of standardization and quality control of stem cell culture in solid extracellular matrices hampers the routine ...

NATURE PUBLISHING GROUP2020

Biotechnologies to tackle the challenge of neoantigen identification

Philippe Renaud, Margaux Catherine Marie Duchamp, George Coukos, Alexandre Harari, Marion Arnaud

Among immune correlates of clinical responses, tumor-specificneoantigens took the spotlight as relevant targets for cancerimmunotherapy. The implementation of pipelines forpersonalized cancer therapy remains challenging due to theprivacy, that is patient-s ...

2020

Tumor-Specific Cytolytic Cd4 T Cells Mediate Protective Immunity Against Human Cancer

David Gfeller, Pedro Romero, Amélie Cachot, Hatice Altug, Margaux Saillard, Xiaokang Li, George Coukos, Yen-Cheng Liu, Alexandre Harari, Alexander Mathis

BMJ PUBLISHING GROUP2020

Measurement of Mitochondrial Mass and Membrane Potential in Hematopoietic Stem Cells and T-cells by Flow Cytometry

Nicola Vannini, Mukul Girotra, Olaia Maria Naveiras Torres-Quiroga, George Coukos, Alexandre Harari

A fine balance of quiescence, self-renewal, and differentiation is key to preserve the hematopoietic stem cell (HSC) pool and maintain lifelong production of all mature blood cells. In recent years cellular metabolism has emerged as a crucial regulator of ...

2019

Microfluidic device performing on flow study of serial cell–cell interactions of two cell populations

Philippe Renaud, Thamani Dahoun, Margaux Catherine Marie Duchamp, George Coukos, Alexandre Harari, Marion Arnaud

In this study we present a novel microfluidic hydrodynamic trapping device to probe the cell–cell interaction between all cell samples of two distinct populations. We have exploited an hydrodynamic trapping method using microfluidics to immobilize a batch ...

2019

The NAD-Booster Nicotinamide Riboside Potently Stimulates Hematopoiesis through Increased Mitochondrial Clearance

Matthias Lütolf, Yannick Lionel Yersin, Vincent Trachsel, Bart Deplancke, Nicola Vannini, Johan Auwerx, Pedro Romero, Carlos Canto Alvarez, Martin Ehrbar, Mukul Girotra, Aurélien Laurent Jean-Charles Oggier, Dongryeol Ryu, Eija Riitta Pirinen, Olaia Maria Naveiras Torres-Quiroga, Pernille Yde Rainer, Gennady Nikitin, Vasco Ledebur de Antas de Campos, Joanna Ratajczak, Loïc Tauzin, Josefine Catharina Pedersen Tratwal, Federico Sizzano, George Coukos, Sonja Giger, Shanti Rojas-Sutterlin, Yang Li, Simone Ragusa

It has been recently shown that increased oxidative phosphorylation, as reflected by increased mitochondrial activity, together with impairment of the mitochondrial stress response, can severely compromise hematopoietic stem cell (HSC) regeneration. Here w ...

CELL PRESS2019

An integrated nanoplasmonic biosensor for monitoring cytokine secretion from single cells

Hatice Altug, Alexander Belushkin, Filiz Yesilköy, Xiaokang Li, George Coukos, Maria Soler Aznar

An innovative nanoplasmonic biosensor was presented for real-time label-free monitoring of cytokine secretion at single-cell resolution. This biosensor is integrated with a uniquely designed microfluidic device that provides a microchamber for cell incubat ...

IEEE2019