Myc controls NK cell development, IL-15-driven expansion, and translational machinery

Area of Science:

• Immunology
• Molecular Biology
• Oncology

Background:

• The transcription factor MYC plays a role in cell proliferation, metabolism, and cancer.
• The specific role and regulation of MYC in natural killer (NK) cells are not well understood.
• NK cells are vital innate immune cells for controlling viral infections and cancer.

Purpose of the Study:

• To investigate the function and regulation of MYC in NK cell development, expansion, and anticancer immunity.
• To elucidate the molecular mechanisms by which MYC influences NK cell biology.

Main Methods:

• Generated mice with NK cell-specific Myc deficiency.
• Utilized cytokine stimulation (IL-15) and pharmacological inhibition of MYC.
• Assessed NK cell development, expansion, translation, and cytotoxic function in vivo and in vitro.
• Analyzed ribosomagenesis and protein translation in NK cells.

Main Results:

• Mice lacking Myc in NK cells showed a severe reduction in NK cell numbers.
• Myc is essential for NK cell development and IL-15-induced expansion.
• Myc deficiency impaired NK cell ribosomagenesis, leading to reduced translation and expansion.
• Pharmacological inhibition of MYC phenocopied these effects in human NK cells.
• Mice with NK cell-specific Myc deficiency exhibited defective anticancer immunity due to reduced NK cell numbers and function.

Conclusions:

• MYC is a critical regulator of NK cell translational fitness, expansion, and effector functions.
• MYC acts as a central node connecting IL-15 signaling to NK cell homeostasis and anticancer immunity.
• Targeting MYC may offer therapeutic strategies for enhancing NK cell-based cancer immunotherapy.