Oral Presentation Melbourne Immunotherapy Network Winter Retreat 2018

Innate Lymphoid Cells in Melanoma: Promising New Targets for Cancer Treatment. (#12)

Nicolas Jacquelot 1 , Gabrielle Belz 1
  1. Walter & Eliza Hall Institute of Medical Research, Melbourne, Parkville

The immune cell infiltration into a tumour is heterogenous. It is composed of multiple cell types that can participate in the response and thus critically dictate the outcome for the patient. Recently discovered innate lymphoid cells (ILCs) are rapidly responding immune cells located in all surface barriers. A key function of this family of cells is to protect our body against pathogens and to maintain tissue homeostasis. ILCs are classified in three main groups based on transcription factors and cytokines they express. We can distinguish IFNg and TNFa-expressing NK cells and ILC1, IL-5 and IL-13-producing ILC2 and IL17 and IL-22-expressing ILC3. This suite of cytokines allows them to play multiple roles by regulating critical biological functions, including wound healing, autoimmunity and, importantly, the removal of cancers. Naturally present in the skin, their involvement in melanoma development and progression is currently unknown. Using pre-clinical models, we assessed their role and functions in this pathology. Firstly, we found that several ILC subsets infiltrate melanoma tumours. Secondly, these cells are functional and produce multiple cytokines that allow them to be major players in shaping the tumour microenvironment. Thirdly, tumour infiltrated ILCs are proliferating cells that express a wide range of immune checkpoints including PD-1, TIGIT, ICOS and CTLA-4. These features suggest that ILCs are likely to be modulated by current immunotherapies and thus impact on melanoma prognosis and a patient’s outcomes. They may also be promising targets for future development of therapies.