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用于预测抗肿瘤疫苗治疗临床反应的免疫监测

Immunological monitoring for prediction of clinical response to antitumor vaccine therapy.

作者信息

Mikhaylova Irina N, Shubina Irina Zh, Chkadua George Z, Petenko Natalia N, Morozova Lidia F, Burova Olga S, Beabelashvili Robert Sh, Parsunkova Kermen A, Balatskaya Natalia V, Chebanov Dmitrii K, Pospelov Vadim I, Nazarova Valeria V, Vihrova Anastasia S, Cheremushkin Evgeny A, Molodyk Alvina A, Kiselevsky Mikhail V, Demidov Lev V

机构信息

N.N. Blokhin Russian Cancer Research Center, Moscow, Russia.

Laboratory of Genetic Engineering, Institute of Experimental Cardiology, Russian Cardiological Research and Production Complex, Moscow, Russia.

出版信息

Oncotarget. 2018 May 11;9(36):24381-24390. doi: 10.18632/oncotarget.25274.

DOI:10.18632/oncotarget.25274
PMID:29849947
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5966268/
Abstract

Immunotherapy has shown promising results in a variety of cancers, including melanoma. However, the responses to therapy are usually heterogeneous, and understanding the factors affecting clinical outcome is still not achieved. Here, we show that immunological monitoring of the vaccine therapy for melanoma patients may help to predict the clinical course of the disease. We studied cytokine profile of cellular Th1 (IL-2, IL-12, IFN-γ) and humoral Th2 (IL-4, IL-10) immune response, vascular endothelial growth factor (VEGFA), transforming growth factor-β 2 (TGF-β 2), S100 protein (S100A1B and S100BB), adhesion molecule CD44 and serum cytokines β2-microglobulin to analyze different peripheral blood mononuclear cell subpopuations of patients treated with dendritic vaccines and/or cyclophosphamide in melanoma patients in the course of adjuvant treatment. The obtained data indicate predominance of cellular immunity in the first adjuvant group of patients with durable time to progression and shift to humoral with low cellular immunity in patients with short-term period to progression (increased levels of IL-4 and IL- 10). Beta-2 microglobulin was differentially expressed in adjuvant subgroups: its higher levels correlated with shorter progression-free survival and the total follow-up time. Immunoregulatory index was overall higher in patients with disease progression compared to the group of patients with no signs of disease progression.

摘要

免疫疗法在包括黑色素瘤在内的多种癌症中已显示出有前景的结果。然而，对治疗的反应通常是异质性的，并且尚未完全了解影响临床结果的因素。在此，我们表明对黑色素瘤患者疫苗治疗的免疫监测可能有助于预测疾病的临床进程。我们研究了细胞Th1（IL-2、IL-12、IFN-γ）和体液Th2（IL-4、IL-10）免疫反应的细胞因子谱、血管内皮生长因子（VEGFA）、转化生长因子-β2（TGF-β2）、S100蛋白（S100A1B和S100BB）、黏附分子CD44以及血清细胞因子β2-微球蛋白，以分析在辅助治疗过程中接受树突状疫苗和/或环磷酰胺治疗的黑色素瘤患者不同外周血单个核细胞亚群。获得的数据表明，在疾病进展持续时间长的第一组辅助治疗患者中细胞免疫占主导，而在疾病进展期短的患者中（IL-4和IL-10水平升高）则转向低细胞免疫的体液免疫。β2-微球蛋白在辅助亚组中差异表达：其较高水平与较短的无进展生存期和总随访时间相关。与无疾病进展迹象的患者组相比

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6f7/5966268/c6f154b446d6/oncotarget-09-24381-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6f7/5966268/b9774d43b010/oncotarget-09-24381-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6f7/5966268/cdcabba72b73/oncotarget-09-24381-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6f7/5966268/c6f154b446d6/oncotarget-09-24381-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6f7/5966268/b9774d43b010/oncotarget-09-24381-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6f7/5966268/cdcabba72b73/oncotarget-09-24381-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6f7/5966268/c6f154b446d6/oncotarget-09-24381-g003.jpg

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本文引用的文献

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