Deplanque Gaël, Shabafrouz Keyvan, Obeid Michel
Département d'Oncologie, Centre Hospitalier Universitaire Vaudois (CHUV), Rue du Bugnon 46, 1011, Lausanne, Switzerland.
Faculté de Médecine Pitié-Salpêtrière, Centre Hospitalo-Universitaire Pitié-Salpêtrière, Université Pierre et Marie Curie, 91 Boulevard de l'Hôpital, 75013, Paris, France.
Cancer Immunol Immunother. 2017 Jul;66(7):833-840. doi: 10.1007/s00262-017-2000-4. Epub 2017 Apr 13.
The abscopal effect, which is the spontaneous regression of tumors or metastases outside the radiation field, occurs rarely in cancer patients. Interestingly, radiotherapy (RT) triggers an immunogenic cell death (ICD) that is able to generate tumor-specific cytotoxic CD8 T cells that are efficient in killing cancer cells. The key question is: why is this "abscopal effect" so uncommon in cancer patients treated with RT? Most probably, the main reason may be related to the highly immunosuppressive tumor microenvironment of well-established tumors that constantly antagonizes the anti-tumor immune responses triggered by RT. In this case, additional or combinatorial immunotherapy is needed to attenuate these immunosuppressive networks and, therefore, substantially increases the efficacy of RT. Here, we describe a potentially promising synergistic radio-immunotherapy "in situ tumor vaccination" protocol by antagonizing the tumor-immunosuppressive microenvironment with a combinatorial approach using local RT and IL-12-based TH1 response augmentation.
远隔效应是指放射野外的肿瘤或转移灶自发消退，在癌症患者中很少发生。有趣的是，放射治疗（RT）会引发免疫原性细胞死亡（ICD），这种死亡能够产生肿瘤特异性细胞毒性CD8 T细胞，这些细胞在杀死癌细胞方面很有效。关键问题是：为什么这种“远隔效应”在接受放疗的癌症患者中如此罕见？很可能，主要原因可能与成熟肿瘤高度免疫抑制的肿瘤微环境有关，这种微环境不断对抗放疗引发的抗肿瘤免疫反应。在这种情况下，需要额外的或联合的免疫疗法来减弱这些免疫抑制网络，从而大幅提高放疗的疗效。在此，我们描述了一种潜在有前景的协同放射免疫疗法“原位肿瘤疫苗接种”方案，该方案通过使用局部放疗和基于白细胞介素-12的辅助性T细胞1型反应增强的联合方法来对抗肿瘤免疫抑制微环境。
