Pre-treatment with chemotherapy can enhance the antigenicity and immunogenicity of tumours by promoting adaptive immune responses.
Pre-treatment with chemotherapy can enhance the antigenicity and immunogenicity of tumours by promoting adaptive immune responses.
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DOI：
10.1038/sj.bjc.6605465
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发表时间：
2010-01-05
影响因子：
8.8
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中科院分区：
文献类型：
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一些癌症患者免疫功能低下，长期以来人们一直认为免疫干预与标准化疗不相容。然而，越来越多的证据表明，标准化疗药物可能会刺激免疫系统和肿瘤的有益变化。我们评估了化疗药物（环磷酰胺、奥沙利铂或吉西他滨）前后肿瘤细胞上人类白细胞抗原 1 (HLA1) 的表达。此外，我们发现化疗应激的肿瘤细胞可能会释放细胞因子，增强树突状细胞 (DC) 和 T 细胞在生长培养基中的相互作用。在这里，我们报道一些化疗药物可以增加肿瘤细胞中 HLA1 的表达，即使表达水平较低。增加与细胞毒性 T 细胞的杀伤有关，而 HLA1 阻断可消除细胞毒性 T 细胞的杀伤作用。此外，T细胞功能（如增殖增加所表明的）由于来自化疗处理的肿瘤的上清液增强了DC成熟和功能而得到增强。有证据表明，适当的化疗药物可以在一定程度上恢复免疫监视。此外，接受某些化疗的肿瘤可能会分泌细胞因子，使 DC 成熟，最终增强 T 细胞反应。
Some cancer patients are immuno-compromised, and it has been long felt that immune-intervention is not compatible with standard chemotherapies. However, increasing evidence suggests that standard chemotherapy drugs may stimulate beneficial changes in both the immune system and tumour. We have assessed the expression of human leucocyte antigen class 1 (HLA1) on tumour cells before and after chemotherapy agents (cyclophosphamide, oxaliplatin or gemcitabine). In addition, we show that chemotherapy-stressed tumour cells may release cytokines that enhance the interactions between dendritic cells (DCs) and T cells into growth media. Here we report that some chemotherapy agents can increase HLA1 expression in tumour cells, even when expression is low. Increases were associated with killing by cytotoxic T cells, which were negated by HLA1-blockade. Furthermore, T-cell function, as indicated by increased proliferation, was enhanced as supernatants derived from tumours treated with chemotherapy augmented DC-maturation and function. There is evidence that a facet of immune surveillance can be restored by appropriate chemotherapy agents. Also, tumours exposed to some chemotherapy may secrete cytokines that can mature DCs, which ultimately enhances T-cell responses.