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.

中文翻译：

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胆固醇调节的细胞硬度可能会增强胃癌干细胞逃避 NK 细胞介导的细胞毒性

胃癌的复发率很高，因此，免疫治疗策略作为一种潜在的治疗策略正在被研究。尽管免疫检查点在免疫治疗中的参与已得到充分研究，但生物力学线索（例如靶细胞硬度）尚未受到相同水平的研究。细胞膜胆固醇含量的变化直接影响肿瘤细胞的硬度。在这里，我们研究了胆固醇对 NK 细胞介导的胃癌干样细胞杀伤作用的影响。我们报告说，具有干细胞样特性的存活肿瘤细胞会提高胆固醇代谢，从而逃避 NK 细胞的细胞毒性。抑制胆固醇代谢可增强 NK 细胞介导的对胃癌干细胞样细胞的杀伤，凸显了提高免疫治疗疗效的潜在途径。这项研究表明癌细胞硬度可能对免疫逃避产生影响，并为增强针对肿瘤的免疫治疗策略提供了见解。