Abstract:
Radiotherapy (RT) can work together with the immune system to eliminate cancer. It can cause immunogenic cell death and facilitate tumor neoantigen presentation and thereby the cross-priming of tumor-specific T-lymphocytes, turning irradiated tumors into in-situ vaccines. Accumulating preclinical and clinical evidence indicates that RT in conjunction with ICB leads to systemic anti-tumor immune responses, thus stimulating interest in using ICB to overcome primary and acquired cancer resistance to radiotherapy. However, the systemic effects (abscopal effects) obtained to date are far from being acceptable for clinical translation. In this context, multiple preclinical mouse models have demonstrated that a variety of immunotherapy agents can be delivered locally to enhance antitumor immunity both in a local and systemic fashion. Using two slightly asynchronous and anatomically distant subcutaneous B16OVA tumors in syngeneic immunocompetent hosts (C57BL/6), we describe the feasibility of a local immunotherapy treatment given in combination with external beam irradiation, which exerts immune-mediated antitumor effects in mice and humans upon intratumoral delivery. With minor variations, the same technique can be easily applied to a variety of mouse transplantable tumors.
摘要:
放射治疗(RT)可以与免疫系统一起消除癌症。它可以引起免疫原性细胞死亡并促进肿瘤新抗原呈递,从而促进肿瘤特异性T淋巴细胞的交叉引发。将照射的肿瘤转化为原位疫苗。越来越多的临床前和临床证据表明,RT与ICB联合导致全身抗肿瘤免疫反应,从而激发了人们对使用ICB克服原发性和获得性癌症对放射疗法的耐药性的兴趣。然而,迄今为止获得的全身性效应(abscopal效应)远不能为临床翻译所接受.在这种情况下,多个临床前小鼠模型已经证明,多种免疫治疗剂可以局部递送,从而以局部和全身方式增强抗肿瘤免疫力.在同基因免疫活性宿主(C57BL/6)中使用两个略微异步且解剖学上远处的皮下B16OVA肿瘤,我们描述了结合外照射给予局部免疫治疗的可行性,在肿瘤内递送后在小鼠和人类中发挥免疫介导的抗肿瘤作用。随着微小的变化,同样的技术可以很容易地应用于各种小鼠可移植的肿瘤。