Department of Surgery, Stanford University School of Medicine, 300 Pasteur Drive, H3591, Stanford, CA 94305-5641, USA.
Cancer Immunol Immunother. 2013 Jun;62(6):1061-71. doi: 10.1007/s00262-013-1417-7. Epub 2013 Apr 18.
Efficacy of cancer chemotherapy is generally believed to be the result of direct drug killing of tumor cells. However, increased tumor cell killing does not always lead to improved efficacy. Herein, we demonstrate that the status of antitumor immunity at the time of chemotherapy treatment is a critical factor affecting the therapeutic outcome in that tumor-bearing mice that possess preexisting antitumor immunity respond to chemotherapy much better than those that do not. Enhancing antitumor immunity before or at the time of chemotherapy-induced antigen release increases subsequent response to chemotherapy significantly. By in vitro and in vivo measurements of antitumor immunity, we found a close correlation between the intensity of antitumor immunity activated by chemotherapy and the efficacy of treatment. Immune intervention with interleukin-12 during the early phase of chemotherapy-induced immune activation greatly amplifies the antitumor response, often resulting in complete tumor eradication not only at the chemo-treated local site, but also systemically. These findings provide additional evidence for an immune-mediated antitumor response to chemotherapy. Further, our results show that timely immune modification of chemotherapy-activated antitumor immunity can result in enhanced antitumor-immune response and complete tumor eradication.
癌症化疗的疗效通常被认为是直接杀死肿瘤细胞的结果。然而，增加肿瘤细胞的杀伤并不总是能提高疗效。在此，我们证明了抗肿瘤免疫的状态在化疗治疗时是一个关键因素，影响治疗结果，即在患有肿瘤的小鼠中，具有预先存在的抗肿瘤免疫的小鼠对化疗的反应要好得多，而那些没有的则反应较差。在化疗诱导抗原释放之前或同时增强抗肿瘤免疫，可以显著增加随后对化疗的反应。通过体外和体内抗肿瘤免疫测量，我们发现化疗激活的抗肿瘤免疫的强度与治疗效果密切相关。在化疗诱导的免疫激活的早期阶段使用白细胞介素 12 进行免疫干预，可以大大增强抗肿瘤反应，通常不仅在化疗治疗的局部部位，而且在全身都能完全消除肿瘤。这些发现为化疗的免疫介导抗肿瘤反应提供了额外的证据。此外，我们的结果表明，及时对化疗激活的抗肿瘤免疫进行免疫修饰，可以增强抗肿瘤免疫反应并完全消除肿瘤。
