在治疗诱导的神经内分泌前列腺癌中BDNF的免疫抑制作用
Yen-Nien Liu1, Wei-Yu Chen2,3, Ming-Kun Liu1
1Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taiwan.
Molecular oncology
|February 21, 2024
概括
抗雄激素剥夺疗法激活白血病抑制因子 (LIF) /LIF受体 (LIFR) 途径,促进前列腺癌 (PCa) 免疫逃避和神经内分泌分化 (NED). 针对LIF/LIFR信号可能克服治疗耐药性.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 免疫学 免疫学 免疫学
背景情况:
- 前列腺癌 (PCa) 的进展涉及瘤微环境 (TME) 内的复杂相互作用.
- 前列腺 stromal 细胞影响PCa 攻击性和免疫逃避,但机制尚未完全理解.
- 矛盾的是,基剥夺疗法 (ADT) 可以促进免疫抑制性TME.
研究的目的:
- 研究白血病抑制因子 (LIF) /LIF受体 (LIFR) 途径在PCa中ADT诱导的免疫抑制和神经内分泌分化 (NED) 中的作用.
- 通过LIF/LIFR信号传导来阐明PCa细胞和前列腺层细胞之间的交叉声.
- 探索针对LIF/LIFR途径的治疗潜力.
主要方法:
- 在ADT后,分析PCa和树皮细胞中LIF/LIFR通路激活.
- 研究LIF/LIFR信号对PCa细胞分化和免疫检查点表达的影响.
- 利用LIFR在树皮细胞中的淘汰来评估其对PCa的影响.
- 测量与LIF/LIFR信号传递和临床结果相关的大脑衍生神经营养因子 (BDNF) 水平.
- 在转移性割抗性PCa (CRPC) 患者样本中对BDNF,PDL1和免疫抑制特征进行关联.
主要成果:
- 在PCa和树皮细胞中,ADT激活了LIF/LIFR信号,产生了免疫抑制的TME.
- 在PCa细胞中的LIF/LIFR激活驱动NED并调高免疫检查点表达 (例如,PDL1).
- 前列腺 stromal 细胞中的 LIFR 表达有助于 PCa NED 和免疫抑制.
- 由ADT诱导的LIF/LIFR信号升级调节BDNF,促进PCa的攻击性和免疫逃避.
- 升高的BDNF水平与转移性CRPC中的PDL1和免疫抑制特征相关.
结论:
- 在前列腺癌中,LIF/LIFR通路是ADT,NED和免疫抑制之间的关键联系.
- 针对LIF/LIFR信号及其下游效应器BDNF可能代表CRPC的新治疗策略.
- 流体细胞介导的LIF/LIFR信号在调节PCa TME和治疗反应方面发挥着重要作用.
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