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Sabina Di Matteo¹, Enrico Munari², Piera Filomena Fiore¹

¹Tumor Immunology Unit, Bambino Gesù Children's Hospital, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Rome, Italy.

Frontiers in immunology

|June 19, 2023

概括

在黑色素瘤进展过程中,Interleukin-15/Interleukin-15受体α (IL-15/IL-15Rα) 复合体的增加. 高水平的可溶性IL-15/IL-15Rα可能代表转移性黑色素瘤患者的免疫逃生机制.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
皮肤病学皮肤病学

背景情况:

黑色素瘤风险与紫外线辐射暴露有关.
紫外线 (UV) 辐射可以诱导细胞因子的产生,可能促进黑色素瘤.
干白素-15 (IL-15) 和它的受体 (IL-15Rα) 综合体正在研究它们在黑色素瘤发展中的作用.

研究的目的:

为了研究Interleukin-15/Interleukin-15受体α (IL-15/IL-15Rα) 复合体在黑色素瘤进展中的作用.
评估IL-15/IL-15Rα复合体在黑色素瘤组织和患者血中的表达.
评估IL-15/IL-15Rα复合体对自然杀手 (NK) 细胞活性的影响,并将表达与患者结果相关联.

主要方法:

在黑色素瘤细胞中对IL-15/IL-15Rα复合物的ex vivo和in vitro分析使用组织微阵列,PCR和流细胞计.
在转移性黑色素瘤患者的血中检测可溶性IL-15/IL-15Rα的ELISA测定.
研究了暴露于可溶性IL-15/IL-15Rα复合物的NK细胞激活和增殖;分析了与黑色素瘤阶段,免疫标志物和整体存活率相关的公共数据集.

主要成果:

随着黑色素瘤从良性瘤向转移性阶段的进展,IL-15的表达增加.
转移性黑色素瘤细胞表达一种可切割的膜结合IL-15 (mbIL-15),而原发性黑色素瘤表达一种耐药的异型.
在26%的转移患者中发现高血水平的可溶性IL-15/IL-15Rα;这个复合物减少了NK细胞的增殖和细胞毒性.
内IL-15和IL-15Rα的产生与T和NK细胞标志物相关,并在II和III阶段黑色素瘤中改善整体存活率.

结论:

膜结合和分泌的IL-15/IL-15Rα复合体在黑色素瘤进展过程中都存在.
虽然最初促进了细胞毒性T和NK细胞,但IV阶段的IL-15/IL-15Rα复合体导致了无能和功能障碍的NK细胞.
在转移性黑色素瘤患者的一个子集中,可溶性IL-15/IL-15Rα的高分泌可能代表了一种新的NK细胞免疫逃生机制.

关键词:

在IL-15中,IL-15是最常见的.复杂的IL15复合体细胞因子细胞因子免疫学免疫学免疫学黑色素瘤是一种黑色素瘤.自然杀手细胞是自然杀手细胞.

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