2007 PROGRAM GRANT - (IMMUNE REGULATION, EFFECTOR FUNCTION AND HUMAN IMMUNOTHERAPY)
Grant number: 454569 | Funding period: 2007 - 2011
The immune system plays an important role in protecting the host from viral and bacterial infections, and inhibits cancer onset and progression. Immune processes proceed through specialised cells in conjunction with soluble factors such as inteferons and interleukins. These soluble factors can regulate the activities of immune cells, and inhibit the growth and survival of aberrant (virus infected, cancer) cells. Unfortunately, the immune system can sometimes lose specificity and attack the host, resulting in autoimmune diseases such as diabetes. This research team has played a vital role in characterising the specific activities of immune cells and the associated factors. Importantly, they a..View full description
Related publications (39)
CDK4/6 Inhibition Promotes Antitumor Immunity through the Induction of T-cell Memory
Emily J Lelliott, Isabella Y Kong, Magnus Zethoven, Kelly M Ramsbottom, Luciano G Martelotto, Deborah Meyran, Joe Jiang Zhu, Matteo Costacurta, Laura Kirby, Jarrod J Sandow, Lydia Lim, Pilar M Dominguez, Izabela Todorovski, Nicole M Haynes, Paul A Beavis, Paul J Neeson, Edwin D Hawkins, Grant A McArthur, Ian A Parish, Ricky W Johnstone
Pharmacologic inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) are an approved treatment for hormone receptor-positive brea..
Serine Biosynthesis Is a Metabolic Vulnerability in FLT3-ITD-Driven Acute Myeloid Leukemia
Stefan Bjelosevic, Emily Gruber, Andrea Newbold, Carolyn Shembrey, Jennifer R Devlin, Simon J Hogg, Lev Kats, Izabela Todorovski, Zheng Fan, Thomas C Abrehart, Giovanna Pomilio, Andrew Wei, Gareth P Gregory, Stephin J Vervoort, Kristin K Brown, Ricky W Johnstone
Internal tandem duplication of the FMS-like tyrosine kinase 3 gene (FLT3-ITD) occurs in 30% of all acute myeloid leukemias (AML). ..
Epigenetic reprogramming of plasmacytoid dendritic cells drives type I interferon-dependent differentiation of acute myeloid leukemias for therapeutic benefit
Jessica Salmon, Izabela Todorovski, Stephin Vervoort, Kym Stanley, Conor Kearney, Luciano Martelotto, Fernando Rossello, Tim Semple, Gisela Mir-Arnau, Magnus Zethoven, Michael Bots, Eva Vidacs, Kate McArthur, Elise Gressier, Nicky de Weerd, Jens Lichte, Madison Kelly, Leonie Cluse, Simon Hogg, Paul Hertzog
Pharmacological inhibition of epigenetic enzymes can have therapeutic benefit, particularly against hematological malignancies. Wh..
CDK13 cooperates with CDK12 to control global RNA polymerase II processivity
Zheng Fan, Jennifer R Devlin, Simon J Hogg, Maria A Doyle, Paul F Harrison, Izabela Todorovski, Leonie A Cluse, Deborah A Knight, Jarrod J Sandow, Gareth Gregory, Andrew Fox, Traude H Beilharz, Nicholas Kwiatkowski, Nichollas E Scott, Ana Tufegdzic Vidakovic, Gavin P Kelly, Jesper Q Svejstrup, Matthias Geyer, Nathanael S Gray, Stephin J Vervoort
The RNA polymerase II (POLII)-driven transcription cycle is tightly regulated at distinct checkpoints by cyclin-dependent kinases ..
JAK2 is dispensable for maintenance of JAK2 mutant B-cell acute lymphoblastic leukemias
Sang-Kyu Kim, Deborah A Knight, Lisa R Jones, Stephin Vervoort, Ashley P Ng, John F Seymour, James E Bradner, Michaela Waibel, Lev Kats, Ricky W Johnstone
Activating JAK2 point mutations are implicated in the pathogenesis of myeloid and lymphoid malignancies, including high-risk B-cel..
CD3(bright) signals on gamma delta T cells identify IL-17A-producing V gamma 6V delta 1( ) T cells
C Paget, MT Chow, NA Gherardin, PA Beavis, AP Uldrich, H Duret, M Hassane, F Souza-Fonseca-Guimaraes, DA Mogilenko, D Staumont-Salle, NK Escalante, GR Hill, P Neeson, DS Ritchie, D Dombrowicz, T Mallevaey, F Trottein, GT Belz, DI Godfrey, MJ Smyth
Interleukin-17A (IL-17A) is a pro-inflammatory cytokine that has an important role at mucosal sites in a wide range of immune resp..
Induction of potent NK cell-dependent anti-myeloma cytotoxic T cells in response to combined mapatumumab and bortezomib
Paul J Neeson, Andy K Hsu, Yin R Chen, Heloise M Halse, Joanna Loh, Reece Cordy, Kate Fielding, Joanne Davis, Josh Noske, Alex J Davenport, Camilla A Lindqvist-Gigg, Robin Humphreys, Tsin Tai, H Miles Prince, Joseph A Trapani, Mark J Smyth, David S Ritchie
There is increasing evidence that some cancer therapies can promote tumor immunogenicity to boost the endogenous antitumor immune ..
The glucocorticoid receptor 1A3 promoter correlates with high sensitivity to glucocorticoid-induced apoptosis in human lymphocytes
Douglas R Liddicoat, Konstantinos Kyparissoudis, Stuart P Berzins, Timothy J Cole, Dale I Godfrey
Glucocorticoids (GCs) are powerful inhibitors of inflammation and immunity. Although glucocorticoid-induced cell death (GICD) is a..
Natural killer T cell defects in multiple myeloma and the impact of lenalidomide therapy
AC Chan, P Neeson, E Leeansyah, K Tainton, H Quach, HM Prince, SJ Harrison, DI Godfrey, D Ritchie, SP Berzins
The causes of multiple myeloma (MM) remain obscure and there are few known risk factors; however, natural killer T (NKT) cell abno..
Ex-vivo analysis of human Natural Killer T cells demonstrates heterogeneity between tissues and within established CD4( ) and CD4(-) subsets
AC Chan, E Leeansyah, A Cochrane, Y d'Udekem d'Acoz, D Mittag, LC Harrison, DI Godfrey, SP Berzins
Our understanding of human type 1 natural killer T (NKT) cells has been heavily dependent on studies of cells from peripheral bloo..
Nfil3 Is a Glucocorticoid-Regulated Gene Required for Glucocorticoid-Induced Apoptosis in Male Murine T Cells
Kirstyn T Carey, Kheng H Tan, Judy Ng, Douglas R Liddicoat, Dale I Godfrey, Timothy J Cole
Glucocorticoids (GCs) have essential roles in the regulation of development, integrated metabolism, and immune and neurological re..
Host immunity contributes to the anti-melanoma activity of BRAF inhibitors
Deborah A Knight, Shin Foong Ngiow, Ming Li, Tiffany Parmenter, Stephen Mok, Ashley Cass, Nicole M Haynes, Kathryn Kinross, Hideo Yagita, Richard C Koya, Thomas G Graeber, Antoni Ribas, Grant A McArthur, Mark J Smyth
The BRAF mutant, BRAF(V600E), is expressed in nearly half of melanomas, and oral BRAF inhibitors induce substantial tumor regressi..
The interaction between murine melanoma and the immune system reveals that prolonged responses predispose for autoimmunity
Shin Foong Ngiow, Bianca von Scheidt, Andreas Moeller, Mark J Smyth, Michele WL Teng
An assessment of antitumor immunity versus autoimmunity as provoked by the specific depletion of Foxp3+ Tregs is now possible with..
The mTORC1 Inhibitor Everolimus Prevents and Treats E mu-Myc Lymphoma by Restoring Oncogene-Induced Senescence
Meaghan Wall, Gretchen Poortinga, Kym L Stanley, Ralph K Lindemann, Michael Bots, Christopher J Chan, Megan J Bywater, Kathryn M Kinross, Megan V Astle, Kelly Waldeck, Katherine M Hannan, Jake Shortt, Mark J Smyth, Scott W Lowe, Ross D Hannan, Richard B Pearson, Ricky W Johnstone, Grant A McArthur
UNLABELLED: MYC deregulation is common in human cancer. IG-MYC translocations that are modeled in Eμ-Myc mice occur in almost all ..
NLRP3 Suppresses NK Cell-Mediated Responses to Carcinogen-Induced Tumors and Metastases
Melvyn T Chow, Jaclyn Sceneay, Christophe Paget, Christina SF Wong, Helene Duret, Juerg Tschopp, Andreas Moeller, Mark J Smyth
The NLRP3 inflammasome acts as a danger signal sensor that triggers and coordinates the inflammatory response upon infectious insu..
Translation inhibitors induce cell death by multiple mechanisms and Mcl-1 reduction is only a minor contributor
LM Lindqvist, I Vikstroem, JM Chambers, K McArthur, M Ann Anderson, KJ Henley, L Happo, L Cluse, RW Johnstone, AW Roberts, BT Kile, BA Croker, CJ Burns, MA Rizzacasa, A Strasser, DCS Huang
There is significant interest in treating cancers by blocking protein synthesis, to which hematological malignancies seem particul..
The immunostimulatory effect of lenalidomide on NK-cell function is profoundly inhibited by concurrent dexamethasone therapy
Andy K Hsu, Hang Quach, Tsin Tai, H Miles Prince, Simon J Harrison, Joseph A Trapani, Mark J Smyth, Paul Neeson, David S Ritchie
Lenalidomide combined with dexamethasone is an effective treatment for refractory/relapsed multiple myeloma (MM). Lenalidomide sti..
Distinct roles in NKT cell maturation and function for the different transcription factors in the classical NF-kappa B pathway
Sanda Stankovic, Raffi Gugasyan, Konstantinos Kyparissoudis, Raelene Grumont, Ashish Banerjee, Philip Tsichlis, Steve Gerondakis, Dale I Godfrey
The nuclear factor (NF)-κB signalling pathway is known to be critical for natural killer T (NKT) cell differentiation; however, th..
Human and mouse perforin are processed in part through cleavage by the lysosomal cysteine proteinase cathepsin L
Spela Konjar, Vivien R Sutton, Sabine Hoves, Urska Repnik, Hideo Yagita, Thomas Reinheckel, Christoph Peters, Vito Turk, Boris Turk, Joseph A Trapani, Natasa Kopitar-Jerala
The pore-forming protein perforin is synthesized as an inactive precursor in natural killer (NK) cells and cytotoxic T lymphocytes..
Ex vivo culture of chimeric antigen receptor T cells generates functional CD8( ) T cells with effector and central memory-like phenotype
P Neeson, A Shin, KM Tainton, P Guru, HM Prince, SJ Harrison, S Peinert, MJ Smyth, JA Trapani, MH Kershaw, PK Darcy, DS Ritchie
The anti-tumor efficacy of adoptively transferred T cells requires their in vivo persistence and memory polarization. It is unknow..
Cathepsin H Is an Additional Convertase of Pro-granzyme B
Michael E D'Angelo, Phillip I Bird, Christoph Peters, Thomas Reinheckel, Joseph A Trapani, Vivien R Sutton
The serine protease granzyme B (GrB) is the most potent proapoptotic cytotoxin of the granule exocytosis pathway of cytotoxic lymp..
Testing the NKT cell hypothesis in lenalidomide-treated myelodysplastic syndrome patients
AC Chan, P Neeson, E Leeansyah, K Tainton, H Quach, HM Prince, DI Godfrey, D Ritchie, SP Berzins
Myelodysplastic syndrome (MDS) comprises a group of clonal bone marrow disorders characterized by ineffective hematopoiesis and in..
IL-21 regulates germinal center B cell differentiation and proliferation through a B cell-intrinsic mechanism
Dimitra Zotos, Jonathan M Coquet, Yang Zhang, Amanda Light, Kathy D'Costa, Axel Kallies, Lynn M Corcoran, Dale I Godfrey, Kai-Michael Toellner, Mark J Smyth, Stephen L Nutt, David M Tarlinton
Germinal centers (GCs) are sites of B cell proliferation, somatic hypermutation, and selection of variants with improved affinity ..
Membrane-bound Fas ligand only is essential for Fas-induced apoptosis
Lorraine A O' Reilly, Lin Tai, Lily Lee, Elizabeth A Kruse, Stephanie Grabow, W Douglas Fairlie, Nicole M Haynes, David M Tarlinton, Jian-Guo Zhang, Gabrielle T Belz, Mark J Smyth, Philippe Bouillet, Lorraine Robb, Andreas Strasser
Fas ligand (FasL), an apoptosis-inducing member of the TNF cytokine family, and its receptor Fas are critical for the shutdown of ..
Type I natural killer T cells suppress tumors caused by p53 loss in mice
Jeremy B Swann, Adam P Uldrich, Serani van Dommelen, Janelle Sharkey, William K Murray, Dale I Godfrey, Mark J Smyth
CD1d-restricted T cells are considered to play a host protective effect in tumor immunity, yet the evidence for a role of natural ..
Immune characterization of an individual with an exceptionally high natural killer T cell frequency and her immediate family
AC Chan, L Serwecinska, A Cochrane, LC Harrison, DI Godfrey, SP Berzins
Natural killer T cells (NKT) are a regulatory subset of T lymphocytes whose frequency in peripheral blood is highly variable withi..
Peripheral NKT Cells in Simian Immunodeficiency Virus-Infected Macaques
Caroline S Fernandez, Angela C Chan, Konstantinos Kyparissoudis, Robert De Rose, Dale I Godfrey, Stephen J Kent
NKT cells are a specialized population of T lymphocytes that have an increasingly recognized role in immunoregulation, including c..
Osteoclast Inhibitory Lectin, an Immune Cell Product That Is Required for Normal Bone Physiology in Vivo
Vicky Kartsogiannis, Natalie A Sims, Julian MW Quinn, Chi Ly, Mirijana Cipetic, Ingrid J Poulton, Emma C Walker, Hasnawati Saleh, Narelle E McGregor, Morgan E Wallace, Mark J Smyth, T John Martin, Hong Zhou, Kong Wah Ng, Matthew T Gillespie
Osteoclast inhibitory lectin (OCIL or clrb) is a member of the natural killer cell C-type lectins that have a described role mostl..
NKT cell development in the absence of the autoimmune regulator gene (Aire)
Lauren A Pitt, Francois-Xavier Hubert, Hamish S Scott, Dale I Godfrey, Stuart P Berzins
Autoimmune regulator gene (Aire)-deficient mice develop an array of autoimmune lesions that reflect failures of immune tolerance. ..
Diverse cytokine production by NKT cell subsets and identification of an IL-17-producing CD4(-)NK1.1(-) NKT cell population
Jonathan M Coquet, Sumone Chakravarti, Konstantinos Kyparissoudis, Finlay W McNab, Lauren A Pitt, Brent S McKenzie, Stuart P Berzins, Mark J Smyth, Dale I Godfrey
NKT cell subsets can be divided based on CD4 and NK1.1 expression and tissue of origin, but the developmental and functional relat..
Residual active granzyme B in cathepsin C-null lymphocytes is sufficient for perforin-dependent target cell apoptosis
Vivien R Sutton, Nigel J Waterhouse, Kylie A Browne, Karin Sedelies, Annette Ciccone, Desiree Anthony, Aulikki Koskinen, Arno Mullbacher, Joseph A Trapani
Cathepsin C activates serine proteases expressed in hematopoietic cells by cleaving an N-terminal dipeptide from the proenzyme upo..