Helper Innate Lymphoid Cells in Human Tumors: A Double-Edged Sword?

Front Immunol. 2020 Jan 29:10:3140. doi: 10.3389/fimmu.2019.03140. eCollection 2019.


Innate lymphoid cells (ILCs) were found to be developmentally related to natural killer (NK) cells. In humans, they are mostly located in "barrier" tissues where they contribute to innate defenses against different pathogens. ILCs are heterogeneous and characterized by a high degree of plasticity. ILC1s are Tbet+, produce interferon gamma and tumor necrosis factor alpha, but, unlike NK cells, are non-cytolytic and are Eomes independent. ILC2 (GATA-3+) secrete type-2 cytokines, while ILC3s secrete interleukin-22 and interleukin-17. The cytokine signatures of ILC subsets mirror those of corresponding helper T-cell subsets. The ILC role in defenses against pathogens is well-documented, while their involvement in tumor defenses is still controversial. Different ILCs have been detected in tumors. In general, the conflicting data reported in different tumors on the role of ILC may reflect the heterogeneity and/or differences in tumor microenvironment. The remarkable plasticity of ILCs suggests new therapeutic approaches to induce differentiation/switch toward ILC subsets more favorable in tumor control.

Keywords: antitumor immune response; checkpoint inhibitors; immunotherapy; innate lymphoid cells; natural killer cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Immunity, Innate / immunology*
  • Lymphocyte Subsets / immunology*
  • Lymphocytes / immunology*
  • Neoplasms / immunology*