Expanding the Horizon of Targeted Radionuclide Therapy: Immunotherapy Combinations and FAP-Targeted Approaches.

IF 5.9 2区 医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
Ayça Arçay Öztürk, Wendy Delbart, Patrick Flamen
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引用次数: 0

Abstract

Targeted radionuclide therapy (TRT) has emerged as a promising cancer treatment modality and is increasingly recognized as an immunomodulatory tool, similar to external beam radiotherapy (EBRT). Both forms of radiation can reshape the tumor immune microenvironment, providing a rationale for their combination with immune checkpoint inhibitors (ICIs) to harness synergistic effects while mitigating immunosuppressive mechanisms. Outcomes of such combinations depend on radiation dose/fractionation, treatment sequencing, target selection, and the choice of immunotherapeutic/radiopharmaceutical agents. Among novel TRT strategies, fibroblast activation protein-TRT (FAP-TRT) stands out for its targeting of cancer-associated fibroblasts (CAFs), key components of the tumor stroma involved in immune evasion and therapy resistance. Unlike conventional TRTs that directly target tumor cells, FAP-TRT acts on CAFs, potentially modulating the tumor microenvironment to enhance the immunomodulatory effects of radiation. This review examines the immunological effects of radiation-via EBRT or TRT-and the rationale for combining TRT with ICIs. We highlight preclinical and clinical studies demonstrating both the synergistic potential and context-specific limitations of TRT-ICI combinations. Emphasis is placed on the emerging role of FAP-TRT in remodeling the tumor microenvironment, converting "cold" tumors into "hot" phenotypes, and enhancing immune infiltration. Preclinical models show synergy between FAP-TRT and ICIs, but challenges remain, including clarifying FAP-TRT's effects on CAF subpopulations, optimizing radiopharmaceutical design, and addressing shared issues with TRT/EBRT-ICI combinations, such as dosing, sequencing, and target selection. The integration of TRT and immunotherapy-particularly FAP-TRT combinations-offers a compelling avenue for precision oncology and warrants further translational and clinical investigation.

扩大靶向放射性核素治疗的视野:免疫治疗组合和fap靶向方法。
靶向放射性核素治疗(TRT)已成为一种很有前景的癌症治疗方式,并越来越被认为是一种免疫调节工具,类似于外部放射治疗(EBRT)。这两种形式的辐射都可以重塑肿瘤免疫微环境,为它们与免疫检查点抑制剂(ICIs)联合使用提供了基本原理,以利用协同效应,同时减轻免疫抑制机制。这种组合的结果取决于辐射剂量/分离、治疗顺序、靶点选择和免疫治疗/放射药物的选择。在新的TRT策略中,成纤维细胞活化蛋白-TRT (FAP-TRT)因其靶向癌症相关成纤维细胞(CAFs)而脱颖而出,CAFs是肿瘤基质中参与免疫逃避和治疗抵抗的关键成分。与直接靶向肿瘤细胞的传统trt不同,FAP-TRT作用于CAFs,可能调节肿瘤微环境以增强辐射的免疫调节作用。本文综述了辐射(通过EBRT或TRT)的免疫效应,以及TRT联合ICIs的基本原理。我们强调临床前和临床研究证明了TRT-ICI联合的协同潜力和具体情况的局限性。重点介绍了FAP-TRT在重塑肿瘤微环境、将“冷”型肿瘤转化为“热”型、增强免疫浸润等方面的新作用。临床前模型显示了FAP-TRT和ICIs之间的协同作用,但挑战仍然存在,包括澄清FAP-TRT对CAF亚群的影响,优化放射性药物设计,以及解决TRT/EBRT-ICI组合的共同问题,如剂量,测序和靶标选择。TRT和免疫治疗的结合,特别是FAP-TRT联合治疗,为精确肿瘤学提供了一条令人信服的途径,值得进一步的转化和临床研究。
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来源期刊
Seminars in nuclear medicine
Seminars in nuclear medicine 医学-核医学
CiteScore
9.80
自引率
6.10%
发文量
86
审稿时长
14 days
期刊介绍: Seminars in Nuclear Medicine is the leading review journal in nuclear medicine. Each issue brings you expert reviews and commentary on a single topic as selected by the Editors. The journal contains extensive coverage of the field of nuclear medicine, including PET, SPECT, and other molecular imaging studies, and related imaging studies. Full-color illustrations are used throughout to highlight important findings. Seminars is included in PubMed/Medline, Thomson/ISI, and other major scientific indexes.
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