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肿瘤浸润免疫细胞作为预测接受伊匹单抗治疗的转移性黑色素瘤患者治疗反应和生存的潜在生物标志物。

Tumor-infiltrating immune cells as potential biomarkers predicting response to treatment and survival in patients with metastatic melanoma receiving ipilimumab therapy.

机构信息

Department of Oncodermatology, National Institute of Oncology, Budapest, Hungary.

1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.

出版信息

Cancer Immunol Immunother. 2018 Jan;67(1):141-151. doi: 10.1007/s00262-017-2072-1. Epub 2017 Oct 7.

Abstract

Monoclonal antibodies targeting immune checkpoints are gaining ground in the treatment of melanoma and other cancers, and considerable effort is made to identify biomarkers predicting the efficacy of these therapies. Our retrospective study was performed on surgical tissue samples (52 lymph nodes and 34 cutaneous/subcutaneous metastases) from 30 patients with metastatic melanoma treated with ipilimumab. Using a panel of 11 antibodies against different immune cell types, intratumoral immune cell densities were determined and evaluated in relation to response to ipilimumab treatment and disease outcome. For most markers studied, median immune cell densities were at least two times higher in lymph node metastases compared to skin/subcutaneous ones; therefore, the prognostic and predictive associations of immune cell infiltration were evaluated separately in the two groups of metastases as well as in all samples as a whole. Higher prevalence of several immune cell types was seen in lymph node metastases of the responders compared to non-responders, particularly FOXP3 cells and CD8 T lymphocytes. In subcutaneous or cutaneous metastases, on the other hand, significant difference could be observed only in the case of CD16 and CD68. Associations of labeled cell densities with survival were also found for most cell types studied in nodal metastases, and for CD16 and CD68 cells in skin/s.c. metastatic cases. Our results corroborate the previous findings suggesting an association between an immunologically active tumor microenvironment and response to ipilimumab treatment, and propose new potential biomarkers for predicting treatment efficacy and disease outcome.

摘要

针对免疫检查点的单克隆抗体在黑色素瘤和其他癌症的治疗中取得了进展,并且正在做出相当大的努力来识别预测这些疗法疗效的生物标志物。我们的回顾性研究是在接受 ipilimumab 治疗的 30 名转移性黑色素瘤患者的手术组织样本(52 个淋巴结和 34 个皮肤/皮下转移)上进行的。使用针对不同免疫细胞类型的 11 种抗体组合,确定了肿瘤内免疫细胞密度,并评估了其与 ipilimumab 治疗反应和疾病结果的关系。对于大多数研究的标志物,淋巴结转移中的免疫细胞密度中位数至少是皮肤/皮下转移的两倍;因此,我们分别在两组转移以及所有样本中评估了免疫细胞浸润的预后和预测相关性。与非应答者相比,应答者的淋巴结转移中几种免疫细胞类型的流行率更高,特别是 FOXP3 细胞和 CD8 T 淋巴细胞。另一方面,在皮下或皮肤转移中,仅在 CD16 和 CD68 的情况下才可以观察到显著差异。在淋巴结转移中,大多数研究的细胞类型以及皮肤/皮下转移性病例中的 CD16 和 CD68 细胞的标记细胞密度与生存之间也存在关联。我们的结果证实了先前的发现,即免疫活性肿瘤微环境与对 ipilimumab 治疗的反应之间存在关联,并提出了新的潜在生物标志物,用于预测治疗效果和疾病结果。

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