Camptothecin Induces PD-L1 and Immunomodulatory Cytokines in Colon Cancer Cells.
Camptothecin Induces PD-L1 and Immunomodulatory Cytokines in Colon Cancer Cells.
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DOI：
10.3390/medicines6020051
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发表时间：
2019-04-24
期刊：
影响因子：
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通讯作者：
Samuel, Temesgen
中科院分区：
文献类型：
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作者：
Bedi, Deepa;Henderson, Henry J;Samuel, Temesgen
背景：免疫疗法改变了各种癌症的治疗选择，但结肠癌没有。目前的检查点阻断方法是无效的，在很大比例的结肠癌病例，需要研究，以阐明其机制，并确定新的目标和战略against it. Methods：在这里，我们研究了程序性死亡配体1（PD-L1），细胞因子和受体的结肠癌细胞暴露于喜树碱（CPT），临床上使用的拓扑异构酶抑制剂的反应。用浓度高达10 M的CPT处理结肠癌细胞，并分析PD-L1和免疫调节细胞因子基因和受体的表达。结果如下：PD-L1是目前各种癌症的免疫治疗靶点，在结肠癌细胞中显示上调，与细胞p53状态无关。在转移源性SW 620细胞中，CPT最广泛地上调具有T细胞吸引或生长因子功能的细胞因子。在这些调节的基因中，SPP 1、IL 1 RN、IL 1A、TNFSF 13 B、OSM和CSF 3具有最大的临床相关性，因为它们的高表达与癌症患者的总体存活率差相关。结论：这些发现强调了在临床前和临床情况下检查拓扑异构酶抑制剂与免疫检查点抑制剂组合的潜在益处的必要性。
: Background: Immunotherapy has changed the options for the treatment of various cancer types, but not colon cancer. Current checkpoint blockade approaches are ineffective in a large proportion of colon cancer cases, necessitating studies to elucidate its mechanisms and to identify new targets and strategies against it. Methods: Here, we examined Programmed Death-Ligand 1(PD-L1), cytokine and receptor responses of colon cancer cells exposed to camptothecin (CPT), a clinically used topoisomerase inhibitor. Colon cancer cells were treated with CPT at concentrations of up to 10 M, and the expressions of PD-L1 and immunoregulatory cytokine genes and receptors were analyzed. Results: PD-L1, a current immunotherapy target for various cancers, was shown to be upregulated in colon cancer cells independent of the cellular p53 status. In metastasis-derived SW620 cells, CPT most extensively upregulated cytokines with T-cell attraction or growth factor functions. Of those modulated genes, SPP1, IL1RN, IL1A, TNFSF13B, OSM, and CSF3 had the most clinical relevance, as their high expression was associated with poor cancer patient overall survival. Conclusions: These findings highlight the need to examine, in preclinical and clinical situations, the potential benefits of combining topoisomerase inhibitors with immune-checkpoint inhibitors.