Radiotherapy Combined with Intralesional Immunostimulatory Agents for Soft Tissue Sarcomas

IF 2.6 3区 医学 Q3 ONCOLOGY Seminars in Radiation Oncology Pub Date : 2024-03-18 DOI:10.1016/j.semradonc.2024.01.001
Chang Su , Soo Kyoung Kim , Charles X. Wang , David G. Kirsch , Arta M. Monjazeb
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引用次数: 0

Abstract

Immunotherapy has shifted the treatment paradigm for many types of cancer. Unfortunately, the most commonly used immunotherapies, such as immune checkpoint inhibitors (ICI), have yielded limited benefit for most types of soft tissue sarcoma (STS). Radiotherapy (RT) is a mainstay of sarcoma therapy and can induce immune modulatory effects. Combining immunotherapy and RT in STS may be a promising strategy to improve sarcoma response to RT and increase the efficacy of immunotherapy. Most combination strategies have employed immunotherapies, such as ICI, that derepress immune suppressive networks. These have yielded only modest results, possibly due to the limited immune stimulatory effects of RT. Combining RT with immune stimulatory agents has yielded promising preclinical and clinical results but can be limited by the toxic nature of systemic administration of immune stimulants. Using intralesional immune stimulants may generate stronger RT immune modulation and less systemic toxicity, which may be a feasible strategy in accessible tumors such as STS. In this review, we summarize the immune modulatory effects of RT, the mechanism of action of various immune stimulants, including toll-like receptor agonists, and data for combinatorial strategies utilizing these agents.

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放疗联合鞘内免疫刺激剂治疗软组织肉瘤
免疫疗法改变了许多类型癌症的治疗模式。遗憾的是,最常用的免疫疗法,如免疫检查点抑制剂(ICI),对大多数类型的软组织肉瘤(STS)疗效有限。放疗(RT)是肉瘤治疗的主要手段,可诱导免疫调节作用。在治疗 STS 时,将免疫疗法和 RT 结合使用可能是一种很有前景的策略,既能改善肉瘤对 RT 的反应,又能提高免疫疗法的疗效。大多数联合策略都采用了抑制免疫抑制网络的免疫疗法,如 ICI。可能由于 RT 的免疫刺激作用有限,这些疗法的效果一般。将 RT 与免疫刺激剂结合使用已取得了很好的临床前和临床效果,但可能会受到全身给药免疫刺激剂毒性的限制。使用鞘内免疫刺激剂可能会产生更强的 RT 免疫调节作用和更小的全身毒性,这可能是 STS 等易发肿瘤的可行策略。在这篇综述中,我们总结了 RT 的免疫调节作用、各种免疫刺激剂(包括收费样受体激动剂)的作用机制以及利用这些药物的组合策略数据。
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来源期刊
CiteScore
5.80
自引率
0.00%
发文量
48
审稿时长
>12 weeks
期刊介绍: Each issue of Seminars in Radiation Oncology is compiled by a guest editor to address a specific topic in the specialty, presenting definitive information on areas of rapid change and development. A significant number of articles report new scientific information. Topics covered include tumor biology, diagnosis, medical and surgical management of the patient, and new technologies.
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