Improving Postoperative Immune Status and Resistance to Cancer Metastasis A Combined Perioperative Approach of Immunostimulation and Prevention of Excessive Surgical Stress Responses
Improving Postoperative Immune Status and Resistance to Cancer Metastasis A Combined Perioperative Approach of Immunostimulation and Prevention of Excessive Surgical Stress Responses
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DOI：
10.1097/sla.0b013e318211d7b5
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发表时间：
2011-04-01
影响因子：
9
通讯作者：
Ben-Eliyahu, Shamgar
中科院分区：
文献类型：
--
作者：
Goldfarb, Yael;Sorski, Liat;Ben-Eliyahu, Shamgar
背景资料：外科手术，包括原发性肿瘤切除术，已被建议抑制免疫能力，并促进术后感染和癌症转移。最近发现，儿茶素和肾上腺素参与了这些过程，并直接促进肿瘤血管生成和侵袭。目的：研究2种互补方法的整合，以减少术后免疫抑制和转移进展：（1）使用CpG-C的围手术期免疫刺激和（2）药理学阻断儿茶酚胺和三尖杉酯碱的肿瘤促进和免疫抑制作用，方法：F344大鼠术前分别给予CpG-C、P+E、CpG-C和P+E两种干预剂或溶媒，并静脉接种同基因MADB 106乳腺癌细胞。抽取血液，收获边缘肺白细胞，并评估NK活性和肺MADB 106肿瘤保留。此外，C57 BL/6小鼠植入同基因B16F10.9黑色素瘤细胞。当肿瘤达到100 mm（3）时，用CpG-C/载体处理小鼠，24小时后沿着用P+E/载体处理切除肿瘤。无复发生存监测afterhears.Results：每一个单独的方案，CpG-C或P+E，显示在大多数指标检查，包括改善长期无复发生存率的改善。最重要的是，联合治疗产生了累加或协同效应，通过不同但互补的机制进一步改善了肺部肿瘤清除率，并增强了NK细胞数量和细胞毒性。采用CpG-C、普萘洛尔和依托度酸，旨在围手术期增强CMI并同时抑制过量的儿茶酚胺和前列腺素反应的治疗，可能成功限制术后免疫抑制和转移进展，比单独使用每种治疗更有效。
Background: Surgical procedures, including primary tumor resection, have been suggested to suppress immune competence and to promote postoperative infections and cancer metastasis. Catecholamines and prostaglandins were recently implicated in these processes, and in directly promoting tumor angiogenesis and invasion.Objective: To examine the integration of 2 complementary approaches to reduce postoperative immunosuppression and metastatic progression: (1) perioperative immunostimulation with CpG-C and (2) pharmacological blockade of the tumor-promoting and immunosuppressing effects of catecholamines and prostaglandins, using propranolol (P) and etodolac (E), respectively.Methods: F344 rats were treated before surgery with CpG-C, P+E, both interventions, or vehicles, and were intravenously inoculated with syngeneic MADB106 mammary adenocarcinoma cells. Blood was withdrawn, marginating-pulmonary leukocytes were harvested, and NK activity and lung MADB106 tumor retention were assessed. In addition, C57BL/6 mice were implanted with syngeneic B16F10.9 melanoma cells. When tumors reached 100mm(3), mice were treated with CpG-C/vehicle, and 24 hours later the tumor was excised along with P+E/vehicle treatment. Recurrence-free survival was monitored thereafter.Results: Each of the regimens alone, CpG-C or P+E, showed improvement in most indices examined, including improved long-term recurrence-free survival rates. Most importantly, the combined treatment yielded additive or synergistic effects, further improving tumor clearance from the lungs and enhancing NK numbers and cytotoxicity via different, but complimentary, mechanisms.Conclusions: Treatment aimed at perioperative enhancement of CMI and simultaneous inhibition of excessive catecholamine and prostaglandin responses, employing CpG-C, propranolol, and etodolac, could be successful in limiting postoperative immunosuppression and metastatic progression, more so than each treatment alone.