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血管内皮生长因子(VEGF)和免疫系统在III/IV期黑色素瘤中作用的前瞻性评估。

A prospective evaluation of the role of Vascular Endothelial Growth Factor (VEGF) and the immune system in stage III/IV melanoma.

作者信息

Agostino Nicole Marie, Saraceni Christine, Kincaid Hope, Shi Wenjing, Nevala Wendy Kay, Markovic Svetomir, Nair Suresh G

机构信息

Lehigh Valley Health Network, Department of Hematology Oncology, John and Dorothy Morgan Cancer Center, 1240 S. Cedar Crest Blvd, Suite 401, Allentown, PA 18103 USA.

Mayo Clinic, Rochester, MN USA.

出版信息

Springerplus. 2015 Apr 17;4:186. doi: 10.1186/s40064-015-0951-5. eCollection 2015.

Abstract

BACKGROUND

The immune system and vascular endothelial growth factor (VEGF) may be influential in melanoma behavior. We performed a prospective, exploratory analysis in 10 stage III and 22 stage IV melanoma patients to observe factors influencing outcomes.

PATIENTS AND METHODS

Patients accrued during 2010 and 2011 were treated according to standard protocols for disease stage. We analyzed selected biomarkers for predictive patterns of clinical response. Survival outcomes were calculated using Kaplan-Meier curves.

RESULTS

Baseline LDH was negatively correlated with length of survival and positively correlated to baseline VEGF in stage IV melanoma patients. We found a positive correlation between peripheral blood Treg concentrations and baseline VEGF in stage IV patients. No stage III patients died during the study period; median survival for stage IV patients was 48 months using a Kaplan-Meier survival curve, which illustrates the enrichment for exceptional stage IV survivors. Six stage IV patients remain disease free, including 4 of the 10 patients who received IL-2 +/- metastatectomy.

CONCLUSIONS

Recent advances in immunotherapy have demonstrated durable therapeutic responses which may favorably impact survival. Examining T-cell characteristics of metastatic melanoma patients may gain further insight into underlying immunomodulation mechanisms to guide improved therapies.

摘要

背景

免疫系统和血管内皮生长因子(VEGF)可能对黑色素瘤的行为有影响。我们对10例III期和22例IV期黑色素瘤患者进行了一项前瞻性探索性分析,以观察影响预后的因素。

患者与方法

2010年和2011年纳入的患者根据疾病分期的标准方案进行治疗。我们分析了选定的生物标志物以寻找临床反应的预测模式。使用Kaplan-Meier曲线计算生存结果。

结果

在IV期黑色素瘤患者中,基线乳酸脱氢酶(LDH)与生存时长呈负相关,与基线VEGF呈正相关。我们发现IV期患者外周血调节性T细胞(Treg)浓度与基线VEGF之间呈正相关。在研究期间没有III期患者死亡;使用Kaplan-Meier生存曲线得出IV期患者的中位生存期为48个月,这表明IV期有一些特殊的长期生存者。6例IV期患者仍无疾病进展,其中包括10例接受白细胞介素-2(IL-2)治疗及/或转移灶切除术患者中的4例。

结论

免疫疗法的最新进展已显示出持久的治疗反应,这可能对生存产生有利影响。研究转移性黑色素瘤患者的T细胞特征可能会进一步深入了解潜在的免疫调节机制,从而指导改进治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/628b/4411400/a51fb4bf17b4/40064_2015_951_Fig1_HTML.jpg

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