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Cambridge Immunology Network



Cytotoxic T-lymphocytes (CTL) kill tumourogenic and virally infected cells by the polarised release of apoptotic-inducing lytic proteins stored within the ‘secretory’ lysosomes of the CTL. Secretion occurs in response to TcR activation on binding to a target cell, and involves morphological and molecular changes within the CTL including movement of the centrosome to the cell surface. These changes result in directed delivery of secretory lysosomes to specific secretory sites on the CTL membrane.

My research as a cell biologist in the laboratory of Professor Gillian Griffiths, takes morphological approaches, including electron and immunofluorescence microscopy, to investigate the cellular events and mechanisms involved in this precisely targeted secretion event.


Key publications: 

Lisci M, Barton PR, Randzavola LO, Ma CY, Marchingo JM, Cantrell DA, Paupe V, Prudent J, Stinchcombe JC, Griffiths GM. Mitochondrial translation is required for sustained killing by cytotoxic T cells. 2021. Science 374:eabe9977

Douanne T, Stinchcombe JC, Griffiths GM. Teasing out function from morphology: Similarities between primary cilia and immune synapses. 2021. J Cell Biol. 220:e202102089

Randzavola LO, Strege K, Juzans M, Asano Y, Stinchcombe JC, Gawden-Bone CM, Seaman MN, Kuijpers TW, Griffiths GM. Loss of ARPC1B impairs cytotoxic T lymphocyte maintenance and cytolytic activity. 2019. J Clin Invest. 129:5600-5614

Stinchcombe JC, Randzavola LO, Angus KL, Mantell JM, Verkade P, Griffiths GM. Mother Centriole Distal Appendages Mediate Centrosome Docking at the Immunological Synapse and Reveal Mechanistic Parallels with Ciliogenesis. 2015. Curr Biol. 25:3239-44.

Ritter AT, Asano Y, Stinchcombe JC, Dieckmann NM, Chen BC, Gawden-Bone C, van Engelenburg S, Legant W, Gao L, Davidson MW, Betzig E, Lippincott-Schwartz J, Griffiths GM. Actin depletion initiates events leading to granule secretion at the immunological synapse. 2015. Immunity. 42:864-76.

Jenkins MR, Stinchcombe JC, Au-Yeung BB, Asano Y, Ritter AT, Weiss A, Griffiths GM. Distinct structural and catalytic roles for Zap70 in formation of the immunological synapse in CTL. 2014. Elife. 3:e01310.

Stinchcombe JC, Salio M, Cerundolo V, Pende D, Arico M, Griffiths GM. Centriole polarisation to the immunological synapse directs secretion from cytolytic cells of both the innate and adaptive immune systems. 2011. BMC Biol. 9:45

Tsun A, Qureshi I, Stinchcombe JC, Jenkins MR, de la Roche M, Kleczkowska J, Zamoyska R, Griffiths GM. Centrosome docking at the immunological synapse is controlled by Lck signalling. 2011. J Cell Biol. 192:663-74

Jenkins MR, Tsun A, Stinchcombe JC, Griffiths GM.The strength of T cell receptor signal controls the polarization of cytotoxic machinery to the immunological synapse. 2009.  Immunity. 31:621-31

Stinchcombe JC, Majorovits E, Bossi G, Fuller S, Griffiths GM. Centrosome polarization delivers secretory granules to the immunological synapse. 2006. Nature. 443:462-5

Clark RH, Stinchcombe JC, Day A, Blott E, Booth S, Bossi G, Hamblin T, Davies EG, Griffiths GM. Adaptor protein 3-dependent microtubule-mediated movement of lytic granules to the immunological synapse. 2003. Nat Immunol. 4:1111-20.

Igakura T, Stinchcombe JC, Goon PK, Taylor GP, Weber JN, Griffiths GM, Tanaka Y, Osame M, Bangham CR. Spread of HTLV-I between lymphocytes by virus-induced polarization of the cytoskeleton. 2003. Science. 299:1713-6.

Stinchcombe JC, Bossi G, Booth S, Griffiths GM. The immunological synapse of CTL contains a secretory domain and membrane bridges. 2001. Immunity. 15:751-61.

Stinchcombe JC, Barral DC, Mules EH, Booth S, Hume AN, Machesky LM, Seabra MC, Griffiths GM. Rab27a is required for regulated secretion in cytotoxic T lymphocytes. 2001. J Cell Biol. 152:825-34.

Stinchcombe JC, Page LJ, Griffiths GM. Secretory lysosome biogenesis in cytotoxic T lymphocytes from normal and Chediak Higashi syndrome patients. 2000. Traffic. 1:435-44.

Hanon E, Stinchcombe JC, Saito M, Asquith BE, Taylor GP, Tanaka Y, Weber JN, Griffiths GM, Bangham CR. Fratricide among CD8(+) T lymphocytes naturally infected with human T cell lymphotropic virus type I. 2000. Immunity. 13:657-64.

Other publications: 

Huhn O, Ivarsson MA, Gardner L, Hollinshead M, Stinchcombe JC, Chen P, Shreeve N, Chazara O, Farrell LE, Theorell J, Ghadially H, Parham P, Griffiths G, Horowitz A, Moffett A, Sharkey AM, Colucci F. Distinctive phenotypes and functions of innate lymphoid cells in human decidua during early pregnancy. 2020. Nat Commun. 11:381.

Kapnick SM, Stinchcombe JC, Griffiths GM, Schwartzberg PL. Inducible T Cell Kinase Regulates the Acquisition of Cytolytic Capacity and Degranulation in CD8+ CTLs. 2017. J Immunol. 198:2699-2711

Dieckmann NM, Frazer GL, Asano Y, Stinchcombe JC, Griffiths GM. The cytotoxic T lymphocyte immune synapse at a glance. 2016. J Cell Sci. 129:2881-6

Stinchcombe JC, Griffiths GM. Communication, the centrosome and the immunological synapse. 2014. Philos Trans R Soc Lond B Biol Sci. 369:20130463.

Lui-Roberts WW, Stinchcombe JC, Ritter AT, Akhmanova A, Karakesisoglou I, Griffiths GM. Cytotoxic T lymphocyte effector function is independent of nucleus-centrosome dissociation. 2012. Eur J Immunol. 42:2132-41

Griffiths GM, Tsun A, Stinchcombe JC. The immunological synapse: a focal point for endocytosis and exocytosis. 2010.   J Cell Biol 189:399-406. Review.

Stinchcombe JC, Griffiths GM. Secretory mechanisms in cell-mediated cytotoxicity. 2007. Annu Rev Cell Dev Biol. 23:495-517. Review.

Santoro A, Cannella S, Bossi G, Gallo F, Trizzino A, Pende D, Dieli F, Bruno G, Stinchcombe JC, Micalizzi C, De Fusco C, Danesino C, Moretta L, Notarangelo LD, Griffiths GM, Aricò M. Novel Munc13-4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis. 2006. J Med Genet. 43:953-60.

Stinchcombe JC, Griffiths GM. The role of the secretory immunological synapse in killing by CD8+ CTL. 2003. Semin Immunol. 15:301-5.

Stinchcombe JC, Griffiths GM. Normal and abnormal secretion by haemopoietic cells. 2001. Immunology. 103:10-6.

Ward DM, Griffiths GM, Stinchcombe JC, Kaplan J. Analysis of the lysosomal storage disease Chediak-Higashi syndrome. 2000. Traffic. 1:816-22.

Bossi G, Stinchcombe JC, Page LJ, Griffiths GM. Sorting out the multiple roles of Fas ligand. 2000. Eur J Cell Biol. 79:539-43.

Stinchcombe JC, Griffiths GM. Regulated secretion from hemopoietic cells. 1999. J Cell Biol. 147:1-6.

Other Professional Activities

Fellow of the Royal Microscopy Society

Not available for consultancy


Departments and institutes: 
Person keywords: 
cell biology
centrosome polarisation
secretory lysosome secretion
immunological synapse