Heterogeneity of NKp46+ ILC in skin pre-cancerous lesions

The family of innate lymphoid cells (ILC) comprises the well-described conventional cytotoxic natural killer cells (NK cells) that patrol lymphoid and non-lymphoid organs to discriminate and eliminate stressed cells (i.e. infected and tumor cells) as well as other ILC subsets that are mainly located in epithelial tissue. How a tumor influences the phenotype and function of those ILC populations at different stages of carcinogenesis is of growing interest. We performed functional and transcriptomic analyses of purified NKp46+ innate lymphoid cells (ILC) from skins, cutaneous lesions and lymph nodes of mice subjected to chemically-induced skin carcinogenesis. We showed that isolated papilloma-derived NKp46+ ILC showed the most divergent gene expression profile compared to their surrounding skin and tumor counterpart. our study indicates that NKp46+ ILC isolated at pre-cancerous stage were enriched in ILC1 subset with less cytotoxic potential than NKp46+ ILC from tumors. These findings revealed a so far unappreciated behavior of NKp46+ ILC at different stages of skin carcinogenesis. FVB/N mice were treated on their shaved-skin twice at week 1 (day 1) and week 7 (day 50) either with the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA, 200nmol per application) diluted in acetone or with acetone alone (naive group). All the mice received the application of the tumor promoter phorbol 12-myristate 13-acetate (PMA, Sigma-Aldrich) diluted in acetone (5nmol per application) twice a week between week 2 and week 6 and between week 8 and 20. Group of mice received only PMA and not DMBA (control group). Cells were extrated from skin lesions, draining lymph nodes and skins and RNA isolation was then performed. Profiling of NKp46+ ILC from the various organs were performed using whole genome mouse microarrays.