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Bioengineering approaches in immunotherapy

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S-acylation by ZDHHC20 targets ORAI1 channels to lipid rafts for efficient Ca2+ signaling by Jurkat T cell receptors at the immune synapse

Françoise Gisou van der Goot Grunberg, Laurence Gouzi Abrami

Efficient immune responses require Ca2+ fluxes across ORAI1 channels during engagement of T cell receptors (TCR) at the immune synapse (IS) between T cells and antigen presenting cells. Here, we show that ZDHHC20-mediated S-acylation of the ORAI1 channel a ...

eLIFE SCIENCES PUBL LTD2021

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The mechanism-of-action of many electrohilic drugs remains poorly understood. Here, the authors use a redox-targeting approach to elucidate the basis for the innate immune cell toxicity of dimethyl fumarate, showing that it modifies Keap1 to trigger mitoch ...

NATURE PORTFOLIO2021

Systematic screening of viral and human genetic variation identifies antiretroviral resistance and immune escape link

Jacques Fellay, Christian Axel Wandall Thorball

Background: Considering the remaining threat of drug-resistantmutations (DRMs) to antiretroviral treatment (ART) efficacy, we investigated how the selective pressure of human leukocyte antigen (HLA)-restricted cytotoxic T lymphocytes drives certain DRMs' e ...

ELIFE SCIENCES PUBLICATIONS LTD2021

Redox-Responsive Polycondensate Neoepitope for Enhanced Personalized Cancer Vaccine

Li Tang, Lixia Wei, Yu Zhao, Xiaomeng Hu

A versatile and highly effective platform remains a major challenge in the development of personalized cancer vaccines. Here, we devised a redox-responsive polycondensate neoepitope (PNE) through a reversible polycondensation reaction of peptide neoantigen ...

2020

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Cancers induced by human papillomaviruses (HPV) should be responsive to immunotherapy by virtue of expressing the immunogenic oncoproteins E6/E7. However, advanced forms of cervical cancer, driven by HPV, are poorly responsive to immune response-enhancing ...

AMER ASSOC CANCER RESEARCH2020

Low-dose photodynamic therapy promotes a cytotoxic immunological response in a murine model of pleural mesothelioma

Paul Joseph Dyson, Etienne Meylan, Julien Robert Rémi Faget, Aspasia Gkasti, Yameng Hao, Maxime Reichenbach

OBJECTIVES: Malignant pleural mesothelioma (MPM) is a deadly disease with limited treatment options. Approaches to enhance patient immunity against MPM have been tested but shown variable results. Previously, we have demonstrated interesting vascular modul ...

OXFORD UNIV PRESS INC2020

Pathogen-mediated balancing selection is regarded as a key driver of host immunogenetic diversity. A hallmark for balancing selection in humans is the heterozygote advantage at genes of the human leukocyte antigen (HLA), resulting in improved HIV-1 control ...

OXFORD UNIV PRESS2020

Adoptive cell transfer of ex vivo expanded regulatory T cells (T-r(egs)) has shown immense potential in animal models of auto- and alloimmunity. However, the effective translation of such T-reg therapies to the clinic has been slow. Because T-reg homeostas ...

2020

CD36-mediated metabolic adaptation supports regulatory T cell survival and function in tumors

Etienne Meylan, Fabien Franco

Depleting regulatory T cells (T-reg cells) to counteract immunosuppressive features of the tumor microenvironment (TME) is an attractive strategy for cancer treatment; however, autoimmunity due to systemic impairment of their suppressive function limits it ...

NATURE PUBLISHING GROUP2020

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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