Charged Particle and Conventional Radiotherapy: Current Implications as Partner for Immunotherapy.
Charged Particle and Conventional Radiotherapy: Current Implications as Partner for Immunotherapy.
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带电粒子和常规放射治疗：作为免疫治疗伙伴的当前意义。
DOI：
10.3390/cancers13061468
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发表时间：
2021-03-23
期刊：
影响因子：
5.2
通讯作者：
Yaromina A
中科院分区：
文献类型：
--
作者：
Marcus D;Lieverse RIY;Klein C;Abdollahi A;Lambin P;Dubois LJ;Yaromina A
免疫治疗为延长癌症患者的生存期，甚至治愈以前无法治疗的恶性肿瘤患者提供了前所未有的机会。临床前和临床研究表明，标准的基于光子的放射治疗和免疫治疗可以协同作用，以促进局部和全身的抗肿瘤免疫，并且仍有很大的改进空间。与光子放射疗法相比，带电粒子放射被认为具有更大的免疫原性潜力，这是由于更致命的未修复损伤、更高的电离密度以及因此更复杂的成簇DNA病变。本文就影响放疗联合免疫治疗成功的因素，如肿瘤的成分、放疗方案和时间表、放射剂量、放射类型等进行综述。此外，研究了支持带电粒子辐射的有利免疫原性特征的理论基础、第一批证据和新见解，包括描述带电粒子引发的免疫相关反应的最佳知识和前瞻性临床试验。放射疗法（RT）已显示干扰炎性信号并通过例如，免疫原性细胞死亡，从而潜在地增强免疫疗法的治疗功效。常规RT主要由高能光子束组成。给予大分割RT方案，例如，通过立体定向体放射疗法（SBRT），越来越多地在临床试验中与癌症免疫疗法联合研究。尽管进行了深入的临床前研究，但用于阐述RT诱导的免疫原性潜力的最佳剂量/分次和剂量方案仍无定论。与联合免疫检查点抑制（ICI）和RT的情况相比，利用其他免疫治疗原理（如过继转移免疫细胞、疫苗接种策略、靶向免疫细胞因子和激动剂）的多模式治疗在临床前和临床环境中的代表性不足。尽管ICI和RT组合的临床成功，例如，虽然局部晚期肺癌的总体生存率有所延长，但大多数研究的癌症实体仍然没有达到治愈效果。荷电粒子RT（PRT）由于其独特的生物学和物理性质而与常规RT相比可以增强肿瘤免疫原性，因此引起了人们的兴趣。然而，PRT联合免疫治疗是否会引起局部和全身的上级抗肿瘤作用需要进一步研究。在这篇综述中，RT在肿瘤微环境中的免疫学效应进行了总结，以了解其对免疫治疗组合的影响。将注意到各种免疫干预措施，已共同管理与RT到目前为止。此外，将检查支持PRT有利免疫原性特征的理论基础和初步证据。
Immunotherapy provides the unprecedented opportunity to prolong the survival of cancer patients and even cure patients with previously untreatable malignancies. Preclinical and clinical studies show that standard photon-based radiotherapy and immunotherapy can synergize in order to promote both local and systemic anti-tumor immunity and that there is still ample room for improvement. Charged particle radiation is thought to have greater immunogenic potential compared to photon radiotherapy due to more lethal unrepaired damage, higher ionization density and thus more complex clustered DNA lesions. In this review, several factors determining the success of radiotherapy combined with immunotherapies, such as composition of the tumor, radiotherapy scheme and schedule, radiation dose, the type of radiation, are addressed. Furthermore, the theoretical basis, first pieces of evidences and new insights supporting a favorable immunogenicity profile of charged particle radiation are examined, including a depiction of best of knowledge for the immune-related responses triggered by charged particles and prospective clinical trials. Radiotherapy (RT) has been shown to interfere with inflammatory signals and to enhance tumor immunogenicity via, e.g., immunogenic cell death, thereby potentially augmenting the therapeutic efficacy of immunotherapy. Conventional RT consists predominantly of high energy photon beams. Hypofractionated RT regimens administered, e.g., by stereotactic body radiation therapy (SBRT), are increasingly investigated in combination with cancer immunotherapy within clinical trials. Despite intensive preclinical studies, the optimal dose per fraction and dose schemes for elaboration of RT induced immunogenic potential remain inconclusive. Compared to the scenario of combined immune checkpoint inhibition (ICI) and RT, multimodal therapies utilizing other immunotherapy principles such as adoptive transfer of immune cells, vaccination strategies, targeted immune-cytokines and agonists are underrepresented in both preclinical and clinical settings. Despite the clinical success of ICI and RT combination, e.g., prolonging overall survival in locally advanced lung cancer, curative outcomes are still not achieved for most cancer entities studied. Charged particle RT (PRT) has gained interest as it may enhance tumor immunogenicity compared to conventional RT due to its unique biological and physical properties. However, whether PRT in combination with immune therapy will elicit superior antitumor effects both locally and systemically needs to be further investigated. In this review, the immunological effects of RT in the tumor microenvironment are summarized to understand their implications for immunotherapy combinations. Attention will be given to the various immunotherapeutic interventions that have been co-administered with RT so far. Furthermore, the theoretical basis and first evidences supporting a favorable immunogenicity profile of PRT will be examined.