Clinical significance of circulating CD33+CD11b+HLA-DR- myeloid cells in Stage-IV melanoma patients treated with ipilimumab
Clinical significance of circulating CD33+CD11b+HLA-DR- myeloid cells in Stage-IV melanoma patients treated with ipilimumab
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接受伊匹单抗治疗的 IV 期黑色素瘤患者中循环 CD33 CD11b HLA-DR- 骨髓细胞的临床意义
DOI：
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
M. Baniyash
中科院分区：
文献类型：
--
作者：
Moshe Sade;Julia Kanterman;Yair Klieger;Eliran Ish;M. Olga;A. Saragovi;Hani Shtainberg;M. Lotem;M. Baniyash
PURPOSE：在包括黑色素瘤在内的各种癌症类型中，高水平的循环髓源性抑制细胞（MDSC）与生存率低下相关。我们研究了循环CD 33 CD 11 bHLA-DR MDSC的频率是否可用作免疫系统监测生物标志物，以预测接受抗CTLA 4（易普利姆玛）治疗的IV期黑色素瘤患者的缓解和生存。实验设计：通过流式细胞术分析来自56名患者和50名健康供体（HD）的外周血样品的CD 33 CD 11bHLA-DR MDSC百分比、NO和hROS水平。我们确定了抗CTLA 4治疗前检测到的MDSC水平和抑制特征是否与患者的反应和总体生存期（OS）相关。结果：与HD相比，黑色素瘤患者具有显著更高水平的具有抑制表型的循环CD 33 CD 11 bHLA-DR MDSC。CTLA-4治疗前低水平的MDSC与客观临床反应、长期存活、T细胞中CD 247表达增加和临床状态改善相关。未观察到对乳酸脱氢酶（LDH）的预测性影响。对56例患者进行Kaplan-Meier和对数秩检验显示，HLA-DR细胞中存在超过55.5%的循环CD 33 CD 11b与显著短OS相关（P<0.003），中位OS为6.5个月，而MDSC频率较低的组中位生存期为15.6个月。结论：我们的研究表明，在接受抗CTLA 4治疗的IV期黑色素瘤患者中，使用CD 33 CD 11bHLA-DR细胞作为预测和预后的生物标志物。这种监测系统可以帮助开发组合模式，靶向抑制环境与iplimumab结合，以促进更好的疾病结果。2020年7月8日© 2016美国癌症研究协会。clincancerres.aacrjournals.org从作者处下载的手稿已经过同行评审并接受出版，但尚未编辑。作者Mandarpt Published OnlineFirst on May 13，2016; DOI：10.1158/1078-0432.CCR-15-3104
PURPORSE: High levels of circulating myeloid derived suppressor cells (MDSCs) in various cancer types, including melanoma, were shown to correlate with poor survival. We investigated whether frequencies of circulating CD33CD11bHLA-DR MDSCs could be used as immune system monitoring biomarkers to predict response and survival of stage-IV melanoma patients treated with anti-CTLA4 (ipilimumab) therapy. EXPERIMENTAL DESIGN: Peripheral blood samples from 56 patients and 50 healthy donors (HD) were analyzed for CD33CD11bHLA-DR MDSC percentage, NO and hROS levels by flow-cytometry. We determined whether MDSC levels and suppressive features detected prior to anti-CTLA4 therapy correlate with the patients’ response and overall-survival (OS). RESULTS: Melanoma patients had significantly higher levels of circulating CD33CD11bHLA-DR MDSCs with suppressive phenotype when compared to HD. Low levels of MDSCs prior to CTLA-4 therapy correlated with an objective clinical response, long-term survival, increased CD247 expression in T-cells and an improved clinical status. No predictive impact was observed for lactate dehydrogenase (LDH). Kaplan-Meier and log-rank tests performed on the 56 patients showed that the presence of more then 55.5% of circulating CD33CD11b out of the HLA-DR cells, were associated with significant short OS (P<0.003), a median of 6.5 months, in comparison to the group showing lower MDSC frequencies, with a median survival of 15.6 months. CONCLUSIONS: Our study suggests the use of CD33CD11bHLA-DR cells as a predictive and prognostic biomarker in stage-IV melanoma patients treated with anti-CTLA4 therapy. This monitoring system may aid in the development of combinatorial modalities, targeting the suppressive environment in conjunction with iplimumab, towards facilitating better disease outcomes. on July 8, 2020. © 2016 American Association for Cancer Research. clincancerres.aacrjournals.org Downloaded from Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 13, 2016; DOI: 10.1158/1078-0432.CCR-15-3104
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影响因子：
5.6
作者：
Greten TF;Manns MP;Korangy F
通讯作者：
Korangy F
影响因子：
2.2
作者：
Kotsakis, Athanasios;Harasymczuk, Malgorzata;Schilling, Bastian;Georgoulias, Vasilis;Argiris, Athanassios;Whiteside, Theresa L.
通讯作者：
Whiteside, Theresa L.
DOI：
10.1056/nejmoa1406498
发表时间：
2014-12-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Snyder A;Makarov V;Merghoub T;Yuan J;Zaretsky JM;Desrichard A;Walsh LA;Postow MA;Wong P;Ho TS;Hollmann TJ;Bruggeman C;Kannan K;Li Y;Elipenahli C;Liu C;Harbison CT;Wang L;Ribas A;Wolchok JD;Chan TA
通讯作者：
Chan TA
影响因子：
6.4
作者：
Jiang, Huanhuan;Gebhardt, Christoffer;Umansky, Viktor
通讯作者：
Umansky, Viktor