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与年龄相关的TREM1/2-表达巨细胞调节促进黑色素瘤的进展和转移

Marzia Scortegagna¹, Rabi Murad¹, Parinaz Bina²

¹Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United States.

Cancer research

|March 24, 2025

概括

衰老促进黑色素瘤转移,通过创造一个免疫抑制瘤微环境. 向TREM2可能会预防老年人肺转移,为黑色素瘤免疫治疗提供新的途径.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
衰老研究研究衰老研究

背景情况:

老龄化是黑色素瘤的重要风险因素,但老年人中增加进展和转移的潜在机制尚不清楚.
瘤微环境的细胞组成和功能可能会因衰老而改变,这可能会促进黑色素瘤的传播.
目前的研究还没有充分探讨瘤微环境中的特定年龄变化如何导致黑色素瘤转移.

研究的目的:

为了研究衰老对黑色素瘤瘤微环境的影响.
为了确定促进黑色素瘤转移的与年龄相关的细胞表型.
评估针对黑色素瘤中特定的年龄相关途径的治疗潜力.

主要方法:

在患有黑色素瘤的年轻和老年小鼠中对瘤微环境的比较分析.
免疫细胞的表型特征,包括巨细胞和T细胞,使用TREM1,TREM2和CD8+T细胞耗尽标记器等标记物.
在年轻和老年小鼠中药理上抑制TREM1和TREM2通路,以评估对黑色素瘤生长和转移的影响.

主要成果:

衰老导致了免疫抑制性瘤微环境,其特点是增加了耐受性TREM2表达性巨细胞和功能障碍,耗尽的CD8+ T细胞.
在老年小鼠中,表达TREM1的profibrotic巨细胞被耗尽.
在年轻小鼠中,TREM1抑制减少了黑色素瘤的生长,但在老年小鼠中却没有.
在老年小鼠中,TREM2抑制有效地预防了肺转移.

结论:

衰老显著改变黑色素瘤瘤的微环境,促进免疫抑制和促进转移潜力.
在老年人群中,TREM2是预防黑色素瘤肺转移的有希望的治疗标.
这些发现凸显了年龄依赖性免疫治疗策略在黑色素瘤治疗中的重要性.

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