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Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells

Yulong Gao1,2, Fernando Souza-Fonseca-Guimaraes1,3,4, Tobias Bald1

  • 1Immunology in Cancer and Infection, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.

Nature Immunology
|August 1, 2017
PubMed

Insights

Tumors evade natural killer (NK) cell detection by converting them into less effective intermediate type 1 innate lymphoid cells (intILC1s) and ILC1s. This TGF-β-driven process hinders anti-tumor immunity.

Area of Science:

  • Immunology
  • Cancer Biology
  • Cellular Plasticity

Background:

  • Tumor cells often evade immune surveillance, particularly by natural killer (NK) cells.
  • The mechanisms by which tumors escape NK cell control are not fully understood.

Purpose of the Study:

  • To investigate the plasticity of NK cells within the tumor microenvironment.
  • To identify mechanisms by which tumors evade NK cell-mediated immunosurveillance.

Main Methods:

  • Global transcriptomic and flow-cytometry analyses were performed.
  • Genetically engineered mouse models were utilized.
  • Antibody neutralization of TNF was employed.

Main Results:

  • NK cells converted into intermediate type 1 innate lymphoid cells (intILC1s) and ILC1s, dependent on TGF-β signaling.
  • intILC1s and ILC1s failed to control tumor growth and metastasis.
  • TNF-producing ILC1s were implicated in immune escape.

Conclusions:

  • Tumor-induced TGF-β signaling drives NK cell conversion to intILC1s and ILC1s.
  • This conversion represents a novel mechanism of tumor immune evasion.
  • Targeting this pathway may enhance anti-tumor immunity.

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