Publications de Alexandre Harari

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

Microfluidic T Cell Selection by Cellular Avidity

Armand Kurum, Li Tang, Alexandre Harari

No T cell receptor (TCR) T cell therapies have obtained clinical approval. The lack of strategies capable of selecting and recovering potent T cell candidates may be a contributor to this. Existing protocols for selecting TCR T cell clones for cell therapi ...

WILEY2022

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

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

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

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

Tumor-associated factors are enriched in lymphatic exudate compared to plasma in metastatic melanoma patients

Melody Swartz, Davide Demurtas, Lambert Charles François Potin, Patricia Corthésy Henrioud, Léa Maillat, Romain Hamelin, Natacha Anne-Sophie Bordry, Maria Anna Sofia Broggi, Alexandre Harari

Liquid biopsies allow monitoring of cancer progression and detection of relapse, but reliable biomarkers in melanoma are lacking. Because secreted factors preferentially drain to lymphatic vessels before dilution in the blood, we hypothesized that lymph sh ...

ROCKEFELLER UNIV PRESS2019

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

Label-free identification of activated T lymphocytes through tridimensional microsensors on chip

Carlotta Guiducci, Elena Bianchi, Enrica Rollo, George Coukos, Enrico Tenaglia, Alexandre Harari

Label-free approaches to assess cell properties ideally suit the requirements of cell-based therapeutics, since they permit to characterize cells with minimal perturbation and manipulation, at the benefit of sample recovery and re-employment for treatment. ...

Elsevier2017