CD103+CD56+ ILCs are associated with an immunosuppressed tumour microenvironment (bulk RNA-Seq)

Immunotherapies have had unprecedented success for multiple cancer types, albeit with variable response rates. Unravelling the complex network of immune cells within the tumour microenvironment (TME) may provide additional insights to enhance anti-tumour immunity and improve clinical response. Here, we identified a CD103-expressing CD56+ ILC subset that were associated with a poor proliferative capacity of tumour-infiltrating lymphocytes (TILs) in culture. We demonstrate that CD103+CD56+ ILCs isolated directly from tumors represent a distinct ILC population that expressed unique surface markers, transcription factor networks, and transcriptomic profiles compared to CD103-CD56+ NK cells. Using multiple approaches, we found that these CD103+CD56+ ILCs were associated with CD8+ T cells with a reduced expression of GZMB. This study identifies 59 a population of CD103+CD56+ ILCs with potentially inhibitory functions, that are associated with a TME that includes CD8+ T cells with poor anti-tumour activity. Further studies focusing on these potentially inhibitory cells may provide insights into understanding the biology of an inhibitory TME.