α与β放射性药物疗法对小鼠前列腺癌的免疫调节作用

Immunomodulatory effects of alpha vs beta radiopharmaceutical therapy in murine prostate cancer.

作者信息

Ferreira Carolina A, Potluri Hemanth K, Mahmoudian Mojdeh, Massey Christopher F, Grudzinski Joseph J, Carston Amanda M, Clemons Nathan B, Idrissou Malick Bio, Thickens Anna S, Rosenkrans Zachary T, Choi Cynthia, Kerr Caroline P, Pinchuk Anatoly N, Kwon Ohyun, Jeffery Justin J, Bednarz Bryan P, Morris Zachary S, Weichert Jamey P, McNeel Douglas G, Hernandez Reinier

机构信息

Departments of Radiology, Pharmacology and Toxicology and Biomedical Engineering, Michigan State University, East Lansing, MI, United States.

Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, United States.

出版信息

Front Immunol. 2025 May 22;16:1563387. doi: 10.3389/fimmu.2025.1563387. eCollection 2025.

DOI:10.3389/fimmu.2025.1563387

PMID:40475779

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12137342/

Abstract

BACKGROUND

Radiation therapy can modulate the tumor microenvironment (TME), influencing antitumor immune responses. This study compared the immunomodulatory effects of alpha-emitting (Ac) and beta-emitting (Lu) radiopharmaceutical therapies (RPT) using NM600 in murine prostate cancer models.

METHODS

We assessed immunological changes in TRAMP-C1 and Myc-CaP tumor models treated with Ac-NM600 or Lu-NM600. Flow cytometry was used to profile immune cell populations, activation markers, and checkpoint molecules, while multiplex assays analyzed cytokine and chemokine expression.

RESULTS

In general, Ac-NM600 elicited stronger immunomodulatory effects than Lu-NM600, including cell line dependent increased CD8/Treg ratios, activation of effector and memory T cells, and depletion of suppressive Tregs and MDSCs. The treatment elevated Th1 cytokines, pro-inflammatory chemokines, and checkpoint molecules like PD-1 on CD8+ T cells and PD-L1 on MDSCs, creating a more "hot" TME.

CONCLUSION

Alpha-emitting Ac-NM600 demonstrated superior ability to enhance antitumor immunity compared to beta-emitting Lu-NM600. These findings support the use of Ac-NM600 in combination with immunotherapies for advanced prostate cancer treatment.

摘要

背景

放射治疗可调节肿瘤微环境（TME），影响抗肿瘤免疫反应。本研究在小鼠前列腺癌模型中比较了使用NM600的发射α粒子（锕）和发射β粒子（镥）的放射性药物疗法（RPT）的免疫调节作用。

方法

我们评估了用锕-NM600或镥-NM600治疗的TRAMP-C1和Myc-CaP肿瘤模型中的免疫变化。流式细胞术用于分析免疫细胞群体、激活标志物和检查点分子，而多重分析则用于分析细胞因子和趋化因子的表达。

结果

总体而言，锕-NM600比镥-NM600引发更强的免疫调节作用，包括细胞系依赖性增加CD8/Treg比率、激活效应性和记忆性T细胞，以及消耗抑制性Treg和MDSC。该治疗提高了Th1细胞因子、促炎趋化因子以及CD8+T细胞上的PD-1和MDSC上的PD-L1等检查点分子的水平，营造了一个更“热”的TME。