1. Academic Validation
  2. Cholesterol-regulated cellular stiffness may enhance evasion of NK cell-mediated cytotoxicity in gastric cancer stem cells

Cholesterol-regulated cellular stiffness may enhance evasion of NK cell-mediated cytotoxicity in gastric cancer stem cells

  • FEBS Open Bio. 2024 Mar 17. doi: 10.1002/2211-5463.13793.
Lijuan Zhu 1 Hongjing Wang 2
Affiliations

Affiliations

  • 1 Department of Radiation Oncology (II), The First Affiliated Hospital of Jinzhou Medical University, China.
  • 2 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinzhou Medical University, China.
Abstract

Gastric Cancer has a high rate of recurrence, and as such, immunotherapy strategies are being investigated as a potential therapeutic strategy. Although the involvement of immune checkpoints in immunotherapy is well studied, biomechanical cues, such as target cell stiffness, have not yet been subject to the same level of investigation. Changes in the Cholesterol content of the cell membrane directly influence tumor cell stiffness. Here, we investigated the effect of Cholesterol on NK cell-mediated killing of gastric Cancer stem-like cells. We report that surviving tumor cells with stem-like properties elevated Cholesterol metabolism to evade NK cell cytotoxicity. Inhibition of Cholesterol metabolism enhances NK cell-mediated killing of gastric Cancer stem-like cells, highlighting a potential avenue for improving immunotherapy efficacy. This study suggests a possible effect of Cancer cell stiffness on immune evasion and offers insights into enhancing immunotherapeutic strategies against tumors.

Keywords

NK cell; SREBP2; cancer stem cells; cholesterol; gastric cancer; immunotherapy.

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