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Age-associated changes in the immune system may influence the response to anti-PD1 therapy in metastatic melanoma patients.

年龄相关的免疫系统变化可能影响转移性黑色素瘤患者对anti-PD1 治疗的反应。

  • 影响因子:4.40
  • DOI:10.1007/s00262-020-02497-9
  • 作者列表:"Kasanen H","Hernberg M","Mäkelä S","Brück O","Juteau S","Kohtamäki L","Ilander M","Mustjoki S","Kreutzman A
  • 发表时间:2020-05-01
Abstract

:Anti-PD1 treatment has improved the survival of metastatic melanoma patients, yet it is unknown which patients benefit from the treatment. In this exploratory study, we aimed to understand the effects of anti-PD1 therapy on the patients' immune system and discover the characteristics that would result in successful treatment. We collected peripheral blood (PB) samples from 17 immuno-oncology-naïve metastatic melanoma patients before and after 1 and 3 months of anti-PD1 therapy. In addition, matching tumor biopsies at the time of diagnosis were collected for tissue microarray. The complete blood counts, PB immunophenotype, serum cytokine profiles, and tumor-infiltrating lymphocytes were analyzed and correlated with the clinical data. Patients were categorized based on their disease control into responders (complete response, partial response, stable disease > 6 months, N = 11) and non-responders (progressive disease, stable disease ≤ 6 months, N = 6). During therapy, the PB natural killer T (NKT) cell frequency, expression of CD25 and CD45RO on cytotoxic natural killer (NK) cells, and serum CXC chemokine levels were significantly increased in responders. Furthermore, higher age together with age-associated characteristics from PB, lower frequency of PB-naïve CD8+ T cells, and elevated levels of serum MCP-4 and OPG were discovered as baseline predictors of treatment response. We therefore propose that in addition to T cells, anti-PD1 treatment is associated with NK- and NKT-cell population dynamics, and that the age-associated characteristics from PB together with older age may contribute to prolonged PFS in anti-PD1-treated melanoma patients.

摘要

: Anti-PD1 治疗改善了转移性黑色素瘤患者的生存,但哪些患者从治疗中获益尚不清楚。在这项探索性研究中,我们旨在了解anti-PD1 治疗对患者免疫系统的影响,并发现成功治疗的特点。我们收集了 17 例免疫-肿瘤初治转移性黑色素瘤患者在anti-PD1 治疗前、治疗后 1 个月和 3 个月的外周血 (PB) 样本。此外,收集诊断时匹配的肿瘤活检用于组织芯片。分析全血细胞计数、PB免疫表型、血清细胞因子谱和肿瘤浸润淋巴细胞,并与临床资料进行相关性。根据其疾病控制情况将患者分为应答者 (完全缓解、部分缓解、稳定疾病> 6 个月,n = 11) 和非应答者 (疾病进展,病情稳定 ≤ 6 个月,n = 6)。治疗期间,应答者PB自然杀伤T (NKT) 细胞频率、细胞毒性自然杀伤 (NK) 细胞上CD25 和CD45RO的表达以及血清CXC趋化因子水平显著升高。此外,较高的年龄以及来自PB的年龄相关特征,较低的PB初治CD8 + T细胞频率,血清MCP-4 和OPG水平升高被发现是治疗反应的基线预测因子。因此,我们提出,除了T细胞,anti-PD1 治疗与NK-和NKT-细胞群体动力学,PB的年龄相关特征与年龄相关可能导致anti-PD1-treated黑色素瘤患者的PFS延长。

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影响因子:2.93
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影响因子:0.96
发表时间:2020-01-01
DOI:10.1097/DAD.0000000000001459
作者列表:["Lang UE","Love NR","Cheung C","McCalmont TH","Kim J"]

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皮肤肿瘤方向

皮肤肿瘤是发生在皮肤的细胞增生性疾病,是一种常见病。发生于皮内或皮下组织的新生物,种类很多,临床上分良性肿瘤和恶性肿瘤。恶性肿瘤可以不断增殖,引起转移,威胁生命,称为皮肤癌。

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