Exploring The Role Of TLR9 In Contributing To Both Cellular And Immune Surveillance During Breast Cancer

Guillaume ROBLOT, International Center for Infectiology Research, France
MAROTEL M. 1 , MOUDOMBI L. 2 , PARROCHE P. 1 , MUSSARD J. 2 , TOUT I. 1 , AINOUZE M. 1 , MICHALLET M. 2 , BENDRISS-VERMARE N. 2 , TREDAN O. 3 , CAUX C. 2 , HASAN U. 1

1 INSERM U1111, International Center for Infectiology Research, Lyon, France
2 INSERM U1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France
3 Department of Medical Oncology, Centre Léon Bérard, Lyon, France

Breast cancer (BC) is the first cancer in females worldwide; from which 500,000 women die each year. Evading the immune system and cell cycle control are two key events associated with cancer development. The activation of Toll Like Receptor 9 (TLR9) (an innate immune sensor mainly expressed on pDCs) leads to the huge production of type I interferon; a critical mediator involved in tumor immunosurveillance and rejection. TLR9 has been reported to be downregulated in several viral induced tumour cells.  In addition, TLR9 responses from tumour associated plasmacytoid dendritic cells (TapDCs) are impaired in ovarian cancer. Based on these results, we hypothesized that TLR9 may contribute to both cellular and immuno-surveillance within the BC. Therefore, we will explore the regulation and decipher the mechanisms of TLR9 dysfunction in mammary carcinoma cells and TApDCs.
Using different tumoral cell lines and an in vitro model of cell senescence, we are currently investigating the role of TLR9 in cell cycle regulation. In parallel, we are generating tools to perform cell cycle analysis and analyze the expression and the role of putative endogenous TLR9 ligands within breast TME.
Overall, this project will allow a comprehensive view of the cellular and immune networks mediated by TLR9 in BC and allow a rational design of innovative therapeutic strategies. The ultimate expected outcome is an improved medical management of the patients from diagnosis to cure.
This study is funded by INCA and is a collaboration between 3 teams, Hasan U. (CIRI), Caux C. (CRCL) and Tredan O. (CLB).