Abstract

Background

Immune-checkpoint inhibitors have shown high objective response rates and long-lasting clinical benefits in several studies, thus revolutionized cancer treatment. Pleomorphic dermal sarcoma (PDS) is a rare cutaneous tumour with local recurrences and distant metastases occurring up to 20% of the cases. With only limited treatment options in advanced stages, there is a strong rationale to explore novel treatments in PDS. In order to achieve this, the profiling of the immune environment in PDS needs to be first explored.

Methods

We collected 14 PDS cases that underwent primary surgical resection at University Hospital Cologne. With formalin-fixed paraffin-embedded (FFPE) materials, we performed a comprehensive immune-phenotype analysis using immunohistochemistry and multiplex gene expression analysis, as well as quantitative assessment of immune cells through quantitative image-analysis. Based on these findings and our preliminary studies, two patients with advanced PDS were enrolled in programmed cell death protein 1 (PD-1) inhibitor therapy.

Results

Eight out of fourteen PDS cases (57%) showed abundance of CD8-positive T-lymphocyte infiltration. Three cases that had above median level of infiltration (hereinafter referred to as CD8-high) displayed high expression levels of immune-related cytokines, immunotherapy response markers, MHC-I expression, and infiltration by PD-L1-, PD-1- and LAG-3-expressing immune cells. The multivariate analysis revealed that CD8-high group highly expressed CD74, LYZ and HLA-B while the CD8-low cases overexpressed CXCL14. In addition, M2 tumor-associated macrophages (TAMs) were localized at the tumor invasion front. Likewise, both patients showed good response to anti-PD-1 therapy in combination with or without radiotherapy and remain in complete remission until now.

Conclusion

We provide the initial comprehensive immune-phenotype profiling of PDS and two representative cases that were successfully treated with immune-checkpoint inhibitor for the first time. These results will aid in further assessment of PDS cases and formulate the qualification criteria for immunotherapy in individuals presenting this rare skin malignancy.

Legal entity responsible for the study

University Hospital Cologne.

Funding

EFRE 2018 (ImmunePredict).

Disclosure

All authors have declared no conflicts of interest.

中文翻译：

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136P分析多形皮肤肉瘤中的肿瘤免疫微环境表明其潜在的免疫治疗效果

抽象的

背景

在多项研究中，免疫检查点抑制剂已显示出较高的客观反应率和长期的临床益处，从而彻底改变了癌症的治疗方法。多形性皮肤肉瘤（PDS）是一种罕见的皮肤肿瘤，在20％的病例中发生局部复发和远处转移。在晚期阶段只有有限的治疗选择，因此有很强的理由去探索PDS中的新型治疗方法。为了实现这一点，需要首先探索PDS中免疫环境的概况。

方法

我们收集了14例在科隆大学医院进行了一次外科手术切除的PDS病例。使用福尔马林固定石蜡包埋（FFPE）材料，我们使用免疫组织化学和多重基因表达分析进行了全面的免疫表型分析，并通过定量图像分析对免疫细胞进行了定量评估。基于这些发现和我们的初步研究，两名晚期PDS患者参加了程序性细胞死亡蛋白1（PD-1）抑制剂治疗。

结果

14例PDS病例中有8例（57％）表现出大量CD8阳性T淋巴细胞浸润。浸润水平高于中位水平的三例（以下称为CD8高）显示免疫相关细胞因子，免疫疗法反应标记物，MHC-1表达以及PD-L1，PD-1-和PD-1浸润的高表达水平。 LAG-3表达免疫细胞。多变量分析显示，高CD8组高表达CD74，LYZ和HLA-B，而低CD8组过表达CXCL14。此外，M2肿瘤相关巨噬细胞（TAMs）位于肿瘤侵袭前沿。同样，两名患者在联合使用或未联合放射治疗的情况下均显示出对抗PD-1治疗的良好反应，直至目前仍完全缓解。

结论

我们提供了PDS的初始全面免疫表型分析，以及两个首次通过免疫检查点抑制剂成功治疗的代表性病例。这些结果将有助于进一步评估PDS病例，并为表现出这种罕见皮肤恶性肿瘤的个体制定免疫疗法的资格标准。

负责研究的法人实体

科隆大学医院。

资金

EFRE 2018（ImmunePredict）。

揭露

所有作者均声明没有利益冲突。