A diversity of novel type-2 innate lymphoid cell subpopulations revealed during tumour expansion

Abstract

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.

A novel type-2 innate lymphoid cell-based immunotherapy for cancer

“…This scarcity of infiltrating immune cells in the untreated tumors indicated a limited immune response within the tumor microenvironment. In stark contrast, in the tumors of animals which underwent ADT treatment using activated tILC2 cells, we detected a significantly higher number of leukocytes within the tumor tissue, as illustrated in Figures 5C-K, and it is well in line with our data provided in Xia et al regarding the enhanced T cells recruitment abilities in activated tILC2s (39). This influx of CD8 + , CD4 + T lymphocytes and eosinophils suggested a robust enrichment of both innate and adaptive immune response against the tumor cells in the treated animals.…”

“…Our previous study (39) demonstrated the ILC2-plasticity during tumor progression on scRNA level, as an acquisition of the new type-1-like immune functions. In the current study, we provide the analysis a set of 32 cytokines and chemokines proteins secreted by tILC2s during neoplasm development, when compared to the protein profile of nILC2 cells.…”

“…Whereas the ADT-induced changes allowed a higher number of eosinophils (Figures 6C, D) to be attracted deeper, closer to the center of the smaller tumor body, suggesting that tILC2-generated products could modify the tumor microenvironment. For instance, the heightened expression of IL-5 by activated tILC2s, as demonstrated in the single-cell RNA data analysis by Xia et al (39) could have diverse impacts on eosinophils, potentially facilitating their infiltration into the tumor mass and thereby contributing to an anti-tumor effect. Thus, the adoptive transfer of tILC2s increased the eosinophilic infiltration into tumor tissue potentially contributing to protective anti-tumor immunity in murine lung carcinoma.…”