Serum Immunoregulatory Proteins as Predictors of Overall Survival of Metastatic Melanoma Patients Treated with Ipilimumab
Serum Immunoregulatory Proteins as Predictors of Overall Survival of Metastatic Melanoma Patients Treated with Ipilimumab
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DOI：
10.1158/0008-5472.can-15-2303
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发表时间：
2015-12-01
期刊：
影响因子：
11.2
通讯作者：
Bahjat, Keith S.
中科院分区：
文献类型：
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作者：
Koguchi, Yoshinobu;Hoen, Helena M.;Bahjat, Keith S.
使用ipilimumab治疗可提高转移性黑色素瘤患者的总存活率(OS)。因为ipilimumab针对的是T淋巴细胞，而不是肿瘤本身，所以疗效可能对治疗时存在的免疫调节因素唯一敏感。我们分析了转移性黑色素瘤患者的血清(273例中有247例，90.4%)，随机分配到接受ipilimumab或gp100肽疫苗的患者。我们在基线上量化了候选生物标记物，并使用多变量分析评估了每个生物标记物之间的相关性。结果在接受ipilimumab治疗的类似患者的独立队列中得到证实(52例中有48例，92.3%)。在控制了基线协变量后，接受ipilimumab治疗的患者中，升高的趋化因子(C-X-C基序)配体11(CXCL11)和可溶性MHC-I类多肽相关链A(SMICA)与OS不良相关[LOG(10)CXCL11：HR，1.88；95%可信区间(CI)，1.14-3.12；P=0.014；LOG(10)SMICA二次效应P=0.066；SMICA(&gT；=247vs.247)：HR，1.75；95%CI，1.02-3.01]。对接受ipilimumab治疗的独立队列的多变量分析证实了log10CXCL11与OS的关联(HR，3.18；95%CI，1.13-8.95；P=0.029)，而SMICA与OS的关联较小[Log10SMICA二次效应P=0.16；SMICA(>；=247vs.247)：HR，1.48；95%CI，0.67-3.27]。在转移性黑色素瘤患者中，高基线CXCL11和SMICA与转移性黑色素瘤患者在接受ipilimumab治疗而不是疫苗治疗后OS差相关。因此，治疗前的CXCL11和SMICA可能是ipilimumab治疗后生存受益的预测因子和治疗靶点。癌症(C)2015年AACR。
Treatment with ipilimumab improves overall survival (OS) in patients with metastatic melanoma. Because ipilimumab targets T lymphocytes and not the tumor itself, efficacy may be uniquely sensitive to immunomodulatory factors present at the time of treatment. We analyzed serum from patients with metastatic melanoma (247 of 273, 90.4%) randomly assigned to receive ipilimumab or gp100 peptide vaccine. We quantified candidate biomarkers at baseline and assessed the association of each using multivariate analyses. Results were confirmed in an independent cohort of similar patients (48 of 52, 92.3%) treated with ipilimumab. After controlling for baseline covariates, elevated chemokine (C-X-C motif) ligand 11 (CXCL11) and soluble MHC class I polypeptide-related chain A (sMICA) were associated with poor OS in ipilimumab-treated patients [log(10) CXCL11: HR, 1.88; 95% confidence interval (CI), 1.14-3.12; P=0.014; and log(10) sMICA quadratic effect P=0.066; sMICA (>= 247 vs. 247): HR, 1.75; 95% CI, 1.02-3.01]. Multivariate analysis of an independent ipilimumab-treated cohort confirmed the association between log10 CXCL11 and OS (HR, 3.18; 95% CI, 1.13-8.95; P=0.029), whereas sMICA was less strongly associated with OS [log10 sMICA quadratic effect P = 0.16; sMICA (>= 247 vs. 247): HR, 1.48; 95% CI, 0.67-3.27]. High baseline CXCL11 and sMICA were associated with poor OS in patients with metastatic melanoma after ipilimumab treatment but not vaccine treatment. Thus, pretreatment CXCL11 and sMICA may represent predictors of survival benefit after ipilimumab treatment as well as therapeutic targets. Cancer (C) 2015 AACR.