Obeid Michel, Panaretakis Theocharis, Tesniere Antoine, Joza Nick, Tufi Roberta, Apetoh Lionel, Ghiringhelli François, Zitvogel Laurence, Kroemer Guido
INSERM, U848, F-94805, Villejuif, France.
Cancer Res. 2007 Sep 1;67(17):7941-4. doi: 10.1158/0008-5472.CAN-07-1622.
In contrast to prior belief, tumor cell apoptosis is not necessarily silent but can be immunogenic. By tracing how anthracyclines and gamma-irradiation trigger immunogenic cell deaths, we found that they were causally connected to the exposure of calreticulin on the tumor cell surface, before apoptosis in the tumor cell itself occurred. Furthermore, we showed that calreticulin exposure was necessary and sufficient to increase proimmunogenic killing by other chemotherapies. Our findings suggest that calreticulin could serve as a biomarker to predict therapy-associated immune responses, and that tactics to expose calreticulin might improve the clinical efficacy of many cancer therapies.
与之前的观点相反，肿瘤细胞凋亡不一定是悄无声息的，而是可能具有免疫原性。通过追踪蒽环类药物和γ射线如何引发免疫原性细胞死亡，我们发现，在肿瘤细胞自身发生凋亡之前，它们与钙网蛋白在肿瘤细胞表面的暴露存在因果关系。此外，我们还表明，钙网蛋白的暴露对于增强其他化疗药物的促免疫原性杀伤作用是必要且充分的。我们的研究结果表明，钙网蛋白可以作为一种生物标志物来预测与治疗相关的免疫反应，并且使钙网蛋白暴露的策略可能会提高许多癌症治疗的临床疗效。
