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Significance NK cells have been observed to be present within most solid tumors, but the antitumor activity of the intratumoral NK cells has been unclear. In this study, we examined the entire spectrum of innate lymphoid cells within primary human tumors and demonstrate that peripheral NK cells in the tumor microenvironment differentiate into heterogeneous cell states, resulting in either a hyporesponsive NK cell subset or a highly active NK cell phenotype that closely resembles intraepithelial ILC1s and that has potent antitumor properties. Importantly, this differentiation into ieILC1-like cells occurs when NK cells are cocultured with epithelial cells, providing important information for NK cell immunotherapy approaches.

Landscape of innate lymphoid cells in human head and neck cancer reveals divergent NK cell states in the tumor microenvironment