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Department of Pathology


PI3K in immunity, infection and cancer

Our group focuses on how a group of enzymes called phosphoinositide 3-kinases (PI3Ks) are used by cells of the immune system to instruct and coordinate defences against pathogens. Cells of the immune system can express up to eight different forms of PI3K, which act as second messenger signalling molecules within cells that control diverse of cellular functions and genetic programmes.

We aim to dissect the unique roles played by individual forms of PI3K with particular focus on their roles in B cells and T cells. We also ask what the effect of inhibiting or enhancing the activity of individual forms of PI3K has on immunity to infections.

Most of our work to date has focused on PI3Kδ. The activation of PI3Kδ is one of the first events that happen inside a T cell or B cell when it first is exposed to a foreign antigen. Because PI3Kδ is expressed at very low levels in other organs in the body, it is thought that targeting PI3K with drugs may be an effective way to suppress immune responses without some of the side effects associated with many immunosuppressive drugs in current use.

We therefore work closely with colleagues in pharmaceutical companies who have developed specific inhibitors against PI3Kδ or other forms of PI3K to help predict and understand the effect of such drugs on the immune system.


Group members: 


PhD students:



Klaus Okkenhaug is Professor of Immunology in the Department of Pathology. He obtained his BSc. in Biochemistry from the University of Victoria, British Columbia, Canada, followed by a PhD. in Immunology from the University of Toronto, where he studied CD28 signalling in Robert Rottapel's lab. In 1999, he moved to London, UK, where he joined Bart Vanhaesebroeck's group at the Ludwig Institute for Cancer Research as a Postdoctoral Fellow, working on the role of the PI3Kδ in immune responses. There he generated the PI3Kδ kinase-dead knock-in mouse, which showed a key role for this PI3K isoform in B cell and T cells. Klaus was a group leader at the Babraham Institute from 2003-2017.

The Okkenhaug lab investigate the role of cell signalling pathways in the immune system, with particular focus on the PI3K family of enzymes. In recent years, we have contributed to the description of a new primary immunodeficiency syndrome caused by activated PI3Kδ mutations (APDS) and  demonstrated that deletion of PI3Kδ in regulatory T cells can unleash potent immune-mediated killing of cancer cells. 


Key publications: 

Selected recent primary research papers:

PI3Kδ Forms Distinct Multiprotein Complexes at the TCR Signalosome in Naïve and Differentiated CD4 + T Cells

DH Luff, K Wojdyla, D Oxley, T Chessa, K Hudson, PT Hawkins, ...

Frontiers in Immunology 12, 415


C5a impairs phagosomal maturation in the neutrophil through phosphoproteomic remodelling. 

Wood, AJ, Vassallo, AM, Ruchaud-Sparagano, MH, Scott, J, Zinnato, C, Gonzalez-Tejedo, C, Kishore, K, D'Santos, CS, Simpson, AJ, Menon, DK, Summers, C, Chilvers, ER, Okkenhaug, K, Conway Morris, A. 

JCI Insight (2020).

DOI: 10.1172/jci.insight.137029.



Loss of Phosphatidylinositol 3-Kinase Activity in Regulatory T Cells Leads to Neuronal Inflammation

Stark AK, Davenport ECM, Patton DT, Scudamore CL, Vanhaesebroeck B, Veldhoen M, Garden OA, Okkenhaug K.

J Immunol. 2020 May 15. Online ahead of print

DOI: 10.4049/jimmunol.2000043



PI3Kδ hyper-activation promotes development of B cells that exacerbate Streptococcus pneumoniae infection in an antibody-independent manner

Stark AK, Chandra A, Chakraborty K, Alam R, Carbonaro V, Clark J, Sriskantharajah S, Bradley G, Richter AG, Banham-Hall E, Clatworthy MR, Nejentsev S, Hamblin JN, Hessel EM, Condliffe AM, Okkenhaug K.

Nat Commun. 2018 Aug 9;9(1):3174. 


Phosphoinositide 3-kinase δ inhibition promotes antitumor responses but antagonizes checkpoint inhibitors

Lim EL, Cugliandolo FM, Rosner DR, Gyori D, Roychoudhuri R, Okkenhaug K.

JCI Insight. 2018 Jun 7;3(11). pii: 120626. doi: 10.1172/jci.insight.120626.

DOI: 10.1172/jci.insight.120626


PI3Kδ promotes CD4(+) T-cell interactions with antigen-presenting cells by increasing LFA-1 binding to ICAM-1

Garçon F and Okkenhaug K.

Immunol Cell Biol. 2016 May;94(5):486-95. doi: 10.1038/icb.2016.1. 

PMCID: PMC4829101 DOI: 10.1038/icb.2016.1


PI3Kδ Regulates the Magnitude of CD8+ T Cell Responses after Challenge with Listeria monocytogenes

Pearce VQ, Bouabe H, MacQueen AR, Carbonaro V, Okkenhaug K.

J Immunol. 2015 Oct 1;195(7):3206-17. 

PMCID: PMC4574522 DOI: 10.4049/jimmunol.1501227


Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer

Ali K, Soond DR, Pineiro R, Hagemann T, Pearce W, Lim EL, Bouabe H, Scudamore CL, Hancox T, Maecker H, Friedman L, Turner M, Okkenhaug K, Vanhaesebroeck B.

Nature. 2014 Jun 19;510(7505):407-411.

PMCID: PMC4501086 DOI: 10.1038/nature13444


Phosphoinositide 3-kinase δ gene mutation predisposes to respiratory infection and airway damage

Angulo I, Vadas O, Garçon F, Banham-Hall E, Plagnol V, Leahy TR, Baxendale H, Coulter T, Curtis J, Wu C, Blake-Palmer K, Perisic O, Smyth D, Maes M, Fiddler C, Juss J, Cilliers D, Markelj G, Chandra A, Farmer G, Kielkowska A, Clark J, Kracker S, Debré M, Picard C, Pellier I, Jabado N, Morris JA, Barcenas-Morales G, Fischer A, Stephens L, Hawkins P, Barrett JC, Abinun M, Clatworthy M, Durandy A, Doffinger R, Chilvers ER, Cant AJ, Kumararatne D, Okkenhaug K, Williams RL, Condliffe A, Nejentsev S.

Science. 2013 Nov 15;342(6160):866-71.

PMCID: PMC3930011 DOI: 10.1126/science.1243292

Other publications: 

Selected Review Articles 

Phosphoinositide 3‐kinase δ is a regulatory T‐cell target in cancer immunotherapy

EL Lim, K Okkenhaug
Immunology. 2019. 157 (3), 210-218. DOI: 10.1111/imm.13082


PI3Kδ and primary immunodeficiencies 

Lucas CL, Chandra A, Nejentsev S, Condliffe AM, Okkenhaug K.

Nat Rev Immunol. 2016 Nov;16(11):702-714. doi: 10.1038/nri.2016.93. Epub 2016 Sep 12. Review.

PMID: 27616589 Free PMC Article 


Okkenhaug K, Graupera M, Vanhaesebroeck B.

Cancer Discov. 2016 Oct;6(10):1090-1105. Epub 2016 Sep 21. Review.

Stark AK, Sriskantharajah S, Hessel EM, Okkenhaug K.

Curr Opin Pharmacol. 2015 Aug;23:82-91. doi: 10.1016/j.coph.2015.05.017. Epub 2015 Jun 18. Review.

Okkenhaug K.

Annu Rev Immunol. 2013;31:675-704. doi: 10.1146/annurev-immunol-032712-095946. Epub 2013 Jan 16. Review.

PMID: 2333095 Free PMC Article


Teaching and Supervisions


Part 1B Biology of Disease (Immunology)

Part II Pathology (Immunology)

Professor of Immunology
Head of the Division of Immunology
Professor Klaus  Okkenhaug

Contact Details

Department of Pathology
University of Cambridge
Tennis Court Road
Takes PhD students
Available for consultancy


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