Cell intrinsic control of CD4 T cell differentiation by cytosolic DNA sensing pathways

Project Information

CD4DNASP

Grant agreement ID: 677251

DOI

10.3030/677251

Project closed

EC signature date 19 May 2016

Start date 1 August 2016

End date 31 July 2021

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 1 500 000,00

EU contribution

€ 1 500 000,00

Coordinated by

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France

Periodic Reporting for period 4 - CD4DNASP (Cell intrinsic control of CD4 T cell differentiation by cytosolic DNA sensing pathways)

Reporting period: 2021-02-01 to 2021-07-31

Summary of the context and overall objectives of the project

Our team is dedicated to finding novel strategies to fight cancer. We are especially focused on strategies that aim to harness the anticancer potential of our immune system. Indeed, in the last ten years, researchers and clinicians have provided the demonstration that in some cancers, therapeutic agents restoring immune responses could successfully treat patients. However, these successes are noted only for a small fraction of cancer patients, underscoring the need to better understand how anticancer immune responses are elicited to develop novel anticancer immunotherapy strategies. We are in that regard interested in a very specific subset of white blood cells, named CD4 T cells. These cells can indeed exert potent anticancer functions when appropriately stimulated. They can for example become IL-9-secreting CD4 T cells (TH9 cells), which have been shown to exert anticancer activities through several ways. Our goal is first to understand the signals that can further enhance CD4 T cell anticancer potential and then use those cells as therapeutic tools. CD4 T cells with a high anticancer potential could be adoptively transferred to patients to favor anticancer immunity and cancer regression.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

We have tested the ability of a molecule that is perceived as a danger signal to CD4 T cells to enhance their activity. We found that their activity was indeed enhanced upon activation of molecules recognizing danger signals. These results were also obtained using human CD4 cells. We have obtained results explaining how this process occurs inside the CD4 T cells upon activation. Because some danger signals can trigger anticancer immune responses in vivo, we have tested the ability of our candidate molecule to favor anticancer immunity. We found that our candidate molecule triggered anticancer immunity through activation of T cells.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

We believe that our candidate molecule could be utilized to enhance the anticancer properties of T cells. This therapeutic strategy could be used in combination with immunomodulation and chemotherapy for optimal anticancer effects.

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