A Diversity of Novel Type-2 Innate Lymphoid Cell Subpopulations Revealed During Tumour Expansion

Type 2 innate lymphoid cells (ILC2s) perform vital functions in orchestrating humoral immune responses, facilitating tissue remodelling, and ensuring tissue homeostasis. Additionally, in a role that has garnered considerably less attention, ILC2s can also enhance Th1-related cytolytic T lymphocyte immune responses against tumours. Studies have thus far generally failed to address the mystery of how one ILC2 cell-type can participate in a multiplicity of functions. Here we utilized single cell RNA sequencing analysis to create the first comprehensive atlas of naïve and tumour-associated lung ILC2s and discover multiple unique subtypes of ILC2s equipped with developmental gene programs that become skewed during tumour expansion favouring inflammation, antigen processing, immunological memory and Th1-related anti-tumour CTL responses. The discovery of these new subtypes of ILC2s challenges current paradigms of ILC2 biology and provides an explanation for their diversity of function. Overall design: Primary ILC2s isolated, purified, enriched and single-cell sequenced at different stages of tumour growth in WT C57BL/6 mice to investigate the immune surveillance dynamics during tumour progression through gene expression changes. Samples include tumour-carrying activated, tumour-carrying non-activated and naive non-activated as control.