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Regulation of integrin function on Treg by PI3K


Department of Pathology

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Prof Klaus Okkenhaug No more applications being accepted Competition Funded PhD Project (UK Students Only)

About the Project

Regulatory T cells (Treg) are a major barrier against effective immunotherapy. We have previously shown that inhibiting PI3Kdelta shifts the balance of the immune system by preferentially inhibiting Treg. It remains unknown; however, exactly why tumour-associated Treg are particularly susceptible to PI3Kdelta inhibition. The successful applicant will test the hypothesis that a major function of PI3Kdelta in Tregs is to regulate the integrin LFA-1. We will determine how kinase-dead or hyperactive mutants of PI3Kdelta affect the recruitment and migration of Tregs within tumours.

Funding Notes

Funding* will cover the student’s stipend at the current Research Council rate and University Fees. The studentship will be funded for three years in the first instance subject to eligibility, with the possibility of additional funding in the fourth year depending on circumstances.

*The studentships are available to students who qualify for Home fees

Applications from ineligible candidates will not be considered.

(http://www.graduate.study.cam.ac.uk/courses/directory/blpapdpth/requirements)

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References

Ali, Khaled, Dalya R. Soond, Roberto Pineiro, Thorsten Hagemann, Wayne Pearce, Ee Lyn Lim, Hicham Bouabe, et al. ‘Inactivation of PI(3)K P110δ Breaks Regulatory T-Cell-Mediated Immune Tolerance to Cancer’. Nature 510, no. 7505 (19 2014): 407–11. https://doi.org/10.1038/nature13444.
Garçon, Fabien, and Klaus Okkenhaug. ‘PI3Kδ Promotes CD4(+) T-Cell Interactions with Antigen-Presenting Cells by IncreasingLFA-1 Binding to ICAM-1’. Immunology and Cell Biology 94, no. 5(2016): 486–95. https://doi.org/10.1038/icb.2016.1.
Lim, Ee Lyn, Fiorella M. Cugliandolo, Dalya R. Rosner, David Gyori, Rahul Roychoudhuri, and Klaus Okkenhaug. ‘Phosphoinositide 3-Kinase δ Inhibition Promotes Antitumor Responses but Antagonizes Checkpoint Inhibitors’. JCI Insight 3, no. 11 (07 2018). https://doi.org/10.1172/jci.insight.120626.
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