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Induction of stress granules alleviates programmed cell death induced by lysosomal damage during NK cell

Yang Liu1,2, Xiaolong Liu1,2, Guangyuan Wu1,2

  • 1NHC Key Laboratory of Cell Transplantation, Harbin Medical University, Harbin, China.

Cell Death Discovery
|May 7, 2026
PubMed

Insights

Cryopreservation of natural killer (NK) cells reduces their viability and function. Pre-treating NK cells with LLOMe stabilizes lysosomes, improving recovery after thawing without impacting anti-cancer efficacy.

Area of Science:

  • Immunology
  • Cell Biology
  • Cancer Therapy

Background:

  • Natural killer (NK) cell therapies offer allogeneic
  • off-the-shelf
  • cancer treatment potential.
  • Cryopreservation negatively impacts NK cell recovery and function, hindering clinical use.
  • Optimizing NK cell cryopreservation is crucial for therapeutic advancement.

Purpose of the Study:

  • To evaluate cryoprotectants for NK cell preservation.
  • To investigate mechanisms of NK cell death post-thaw.
  • To identify strategies for improving NK cell cryopreservation outcomes.

Main Methods:

  • Assessment of NK cell viability, ATP levels, and cytotoxicity post-thaw.
  • Transmission electron microscopy, flow cytometry, and Western blot analysis.
  • Investigation of cryoprotectants (CryoStor 10, ZKCELL FM-01, FBS + DMSO) and death inhibitors.
  • Evaluation of centrifugation effects and lysosomal stability.
  • Pretreatment with low-dose LLOMe to induce stress granules.

Main Results:

  • Cryopreservation significantly reduced NK cell viability and function compared to fresh cells.
  • A complex cell death pathway was observed, partially mitigated by death inhibitors.
  • Lysosomal stability was identified as critical for NK cell survival post-thaw.
  • LLOMe pretreatment stabilized lysosomes, enhanced cell recovery, and maintained effector function.

Conclusions:

  • Current cryopreservation methods compromise NK cell therapeutic potential.
  • Lysosomal stabilization is a key target for improving NK cell cryopreservation.
  • LLOMe pretreatment offers a promising strategy to enhance NK cell cryopreservation for clinical applications.

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