Publications de George Coukos | EPFL Graph Search

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

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

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

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

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

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

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

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

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, George Coukos, Fabrizio Benedetti, Ioannis Xenarios, Alexandre Harari

2021

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

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

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

Bruno Emanuel Ferreira De Sousa Correia, George Coukos, 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