Obesity Does Not Exacerbate the Protumorigenic Systemic Environment in Sarcoma Subjects.
Obesity Does Not Exacerbate the Protumorigenic Systemic Environment in Sarcoma Subjects.
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DOI：
10.4049/immunohorizons.1700001
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发表时间：
2017-06-01
期刊：
影响因子：
--
通讯作者：
Norian LA
中科院分区：
文献类型：
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作者：
Buchta CM;Boi SK;Miller BJ;Milhem MM;Norian LA
肉瘤是一种罕见但致命的肿瘤类型，占成人实体恶性肿瘤的1%以下和儿童恶性肿瘤的15%左右。尽管对其他实体瘤的免疫治疗正在积极研究中，但对肉瘤患者的免疫治疗仍缺乏进展。为了更好地了解肉瘤患者的全身免疫环境，我们对未接受治疗的局部高级别肉瘤患者的血清细胞因子、趋化因子和致瘤因子进行了详细的多重分析。由于肥胖在美国是一个主要的医疗保健问题，我们在我们的肉瘤受试者队列中额外检查了肥胖对血清蛋白谱的影响。我们发现，系统宿主环境发生了深刻的改变，有利于肿瘤的进展，表皮生长因子、血管生成素-2、血管内皮生长因子A、IL-6、IL-8和MIP-1β均相对于无肿瘤对照组升高（均p < 0.05）。令人惊讶的是，我们发现肥胖并没有加剧这种蛋白的形成，因为表皮生长因子和IL-8随着受试者体重指数的增加而下降（与正常或超重受试者相比，p < 0.05）。与th2相关的细胞因子IL-4、IL-5和IL-13也在肥胖的情况下下降。因此，尽管肉瘤患者的全身环境有利于肿瘤进展，但肥胖不会进一步加剧致瘤因子的产生。
Sarcomas are a rare but fatal tumor type that accounts for <1% of adult solid malignancies and ~15% of childhood malignancies. Although the use of immunotherapy is being actively investigated for other solid tumors, advances in immunotherapy for sarcoma patients are lacking. To better understand the systemic immune environment in sarcoma patients, we performed a detailed multiplex analysis of serum cytokines, chemokines, and protumorigenic factors from treatment-naive subjects with localized, high-grade sarcoma. Because obesity is a major healthcare issue in the United States, we additionally examined the effects of obesity on serum protein profiles in our sarcoma subject cohort. We found that the systemic host environment is profoundly altered to favor tumor progression, with epidermal growth factor, angiopoietin-2, vascular endothelial growth factor A, IL-6, IL-8, and MIP-1β all increased relative to tumor-free controls (all p < 0.05). Surprisingly, we found that obesity did not exacerbate this protumorigenic profile, as epidermal growth factor and IL-8 decreased with increasing subject body mass index (both p < 0.05 versus normal or overweight subjects). The Th2-related cytokines IL-4, IL-5, and IL-13 were also decreased in the presence of obesity. Thus, although the systemic environment in sarcoma subjects favors tumor progression, obesity does not further aggravate the production of protumorigenic factors.