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.

中文翻译：

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放疗联合病灶内免疫刺激剂治疗软组织肉瘤

免疫疗法改变了多种癌症的治疗模式。不幸的是，最常用的免疫疗法，例如免疫检查点抑制剂（ICI），对大多数类型的软组织肉瘤（STS）的疗效有限。放射治疗（RT）是肉瘤治疗的主要手段，可以诱导免疫调节作用。在 STS 中将免疫疗法和放疗结合起来可能是改善肉瘤对放疗的反应并提高免疫疗法疗效的有前途的策略。大多数联合策略都采用了免疫疗法，例如 ICI，可以解除免疫抑制网络的抑制。这些研究仅取得了有限的结果，可能是由于放疗的免疫刺激作用有限。将放疗与免疫刺激剂相结合已取得了有希望的临床前和临床结果，但可能受到免疫刺激剂全身给药的毒性的限制。使用病灶内免疫刺激剂可能会产生更强的 RT 免疫调节作用和更少的全身毒性，这对于 STS 等易触及的肿瘤可能是一种可行的策略。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 Toll 样受体激动剂）的作用机制，以及利用这些药物的组合策略的数据。