Locher Clara, Rusakiewicz Sylvie, Tesnière Antoine, Ghiringhelli François, Apetoh Lionel, Kroemer Guido, Zitvogel Laurence
Institut National de la Santé et de la Recherche Médicale, U805, Villejuif, France.
Ann N Y Acad Sci. 2009 Sep;1174:51-60. doi: 10.1111/j.1749-6632.2009.04940.x.
Conventional cancer treatments mediate their effects via the direct elimination of tumor cells. Nonetheless, recent evidence indicates that radiotherapy and some chemotherapeutic agents can also induce specific immune responses that contribute to therapeutic outcomes. Two major tumor-intrinsic changes that determine the immune response against tumors have been identified: the translocation of calreticulin to the plasma membrane and the release of high-mobility group box 1 protein. Together, these changes improve engulfment and processing of apoptotic bodies by dendritic cells, which are involved in the cross-priming of antitumor T lymphocytes in vivo. We review these two molecular mechanisms that dictate the radio/chemotherapy-elicited antitumor immune response and discuss how this knowledge can be clinically exploited to predict and also ameliorate the success of chemo/radiotherapy.
传统的癌症治疗方法通过直接消除肿瘤细胞来发挥作用。然而,最近的证据表明,放疗和一些化疗药物也能诱导特定的免疫反应,从而有助于治疗效果。已经确定了两种决定抗肿瘤免疫反应的主要肿瘤内在变化:钙网蛋白向质膜的转位和高迁移率族蛋白B1的释放。这些变化共同改善了树突状细胞对凋亡小体的吞噬和处理,而树突状细胞参与体内抗肿瘤T淋巴细胞的交叉启动。我们综述了这两种决定放疗/化疗引发的抗肿瘤免疫反应的分子机制,并讨论了如何在临床上利用这些知识来预测并提高化疗/放疗的成功率。