Research highlights

The Cellular Immunology Research Group is interested in how the ultraviolet part of the solar spectrum alters the immune outcome so that immune regulation or suppression occurs instead of immune activation. These studies are important because immune suppression is one of the main contributors to skin cancer development. Understanding the cellular and molecular mechanisms underlying immune regulation is also important for other diseases such as autoimmune disorders and for the success of immunisation strategies.

Overview of research program

The prevalence of skin cancer continues to rise despite increased awareness of the need to protect ourselves from the prime cause of skin cancer – sunlight. Clearly, preventing skin cancer by limiting the amount and type of sun exposure has been insufficient. In order to understand carcinogenesis we must study the mechanisms that allow tumours to establish – that is DNA damage and suppression of anti-tumour immunity. This is the core focus of Dr Scott Byrne and his group.
Dr Byrne’s team is investigating the mechanisms by which sunlight suppresses anti-tumour immune responses. In order for skin cancer to develop, two things must occur: DNA damage to cells, and suppression of the host anti-tumour immune response. The ultraviolet (UV) wavebands in sunlight cause both of these; sunlight is therefore one of the most potent and significant environmental carcinogens to which humans are exposed.
While the DNA damaging properties of UV are relatively well characterised, the mechanisms by which UV suppresses the immune system are not understood. Dr Byrne and his team are investigating the role of UV-induced factors (called cytokines) in activating specific immune cells with regulatory activities.
Understanding the cellular and molecular pathways involved in skin cancer growth will greatly facilitate the design of novel therapeutics aimed at preventing UV-induced suppression of anti-tumour immune responses. This will make a major contribution to reducing the incidence of skin cancer in Australia.

Major funding sources

Cancer Institute NSW Career Development and Support Fellowship: 2008-2011: The role of migrating mast cells in activating regulatory populations and suppressing anti-tumour immune responses. S.N. Byrne

Selected publications

1. Michael Stapelberg, Rohan Williams, Scott N. Byrne and Gary Halliday 2009. The alternative complement pathway seems to be a UVA sensor that leads to systemic immunosuppression. Journal of Investigative Dermatology. 129(11) 2694-2701.
2. Scott N. Byrne, Alberto Y. Limón-Flores and Stephen E. Ullrich. 2008. Mast cell migration from the skin to the draining lymph nodes upon UV-irradiation represents a key step in the induction of immune suppression. Journal of Immunology 180(7) 4648-4655.
3. Scott N. Byrne, Matthew Knox and Gary Halliday. 2008. TGFβ1 is responsible for skin tumour infiltration by macrophages enabling the tumours to escape immune destruction. Immunology and Cell Biology 86(1) 92-97
4. Atsushi Fukunaga, Noor M. Khaskhley, Coimbatore S. Sreevidya, Scott N. Byrne and Stephen E. Ullrich. 2008. Dermal dendritic cells, and not Langerhans cells, play an essential role in inducing an immune response. Journal of Immunology 180(5) 3057-3064.
5. Yumi Matsumura*, Scott N. Byrne*, Dat X. Nghiem, Yasuko Miyahara, and Stephen E. Ullrich. 2006 A role for inflammatory mediators in the induction of immunoregulatory B cells. * Both of these authors contributed equally to this work. Journal of Immunology 177(7) 4810-4817
6. Scott N. Byrne and Gary M. Halliday. 2005. B cells activated in lymph nodes in response to Ultraviolet-irradiation or by IL-10 inhibit Dendritic Cell induction of immunity. Journal of Investigative Dermatology. 124(3) 570-578.
7. Scott N. Byrne and Gary M. Halliday. 2003 Phagocytosis by Dendritic Cells Rather than MHC IIhigh Macrophages is Associated with Skin Tumour Regression International Journal of Cancer 106(5) 736-744.
8. Scott N. Byrne and Gary M. Halliday. 2003. High Levels of Fas Ligand and MHC Class II in the Absence of CD80 or CD86 Expression and a Decreased CD4(+) T cell Infiltration, enables Skin Tumours to Progress Cancer Immunology, Immunotherapy 52(6) 396-402
9. Scott N. Byrne, Nicole Spinks and Gary M. Halliday. 2002. Ultraviolet-A Irradiation of C57BL/6 Mice Suppresses Systemic Contact Hypersensitivity or Enhances Secondary Immunity Depending on Dose The Journal of Investigative Dermatology 119(4) 858-864
10. Scott N. Byrne, Gary M. Halliday, Linda J. Johnston & Nicholas JC King. 2001. IL-1β but not TNF is involved in West Nile Virus-Induced Langerhans cell migration from the skin in C57BL/6 mice The Journal of Investigative Dermatology, 117(3) 702-9.