Tulokas Sanni K A, Juteau Susanna, Mäkelä Siru P, Välimäki Katja E, Pellinen Teijo, Hernberg Micaela M
Department of Oncology, Comprehensive Cancer Centre, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Pigment Cell Melanoma Res. 2025 Jul;38(4):e70040. doi: 10.1111/pcmr.70040.
As effective melanoma treatments have become available, utilizing isolated limb perfusion (ILP) to treat unresectable melanoma limited to the limb has decreased. However, some patients still receive long-term benefits from ILP. We aimed to identify features of the pretreatment tumor microenvironment (TME) to identify patients who may benefit from ILP. Pretreatment metastatic melanoma samples from 22 patients treated at Helsinki University Hospital with ILP from 2008 to 2018 were analyzed with multiplex immunohistochemistry (mIHC) and digital image analysis. Antibody panels evaluated the proportions of immune cells in the intratumoral and extratumoral compartments. We examined whether treatment response and median progression-free survival (PFS) after ILP correlated to findings in the TME. A statistically significant positive correlation was found between PFS and lower immune cell infiltrations in the intratumoral compartment (CD3+, CD4+, and CD11c+ cells), and increased numbers of immune cells in the extratumoral compartment were associated with longer PFS (CD3+, CD4+, CD8+, all expressing PD-1). Furthermore, the distribution of some immune cell subsets correlated with complete treatment response (PD-1/PD-L1-positive CD4+ and PD-1-positive CD8+ cells). Our results suggest that patients may have a better ILP outcome if the metastases exhibit a lower distribution of specific immune cell subtypes intratumorally and a higher extratumoral distribution of some immune cell subtypes.
随着有效的黑色素瘤治疗方法的出现，利用隔离肢体灌注（ILP）治疗局限于肢体的不可切除黑色素瘤的情况已有所减少。然而，一些患者仍能从ILP中获得长期益处。我们旨在确定预处理肿瘤微环境（TME）的特征，以识别可能从ILP中获益的患者。对2008年至2018年在赫尔辛基大学医院接受ILP治疗的22例患者的预处理转移性黑色素瘤样本进行了多重免疫组织化学（mIHC）和数字图像分析。抗体组评估了肿瘤内和肿瘤外区域免疫细胞的比例。我们研究了ILP后的治疗反应和中位无进展生存期（PFS）是否与TME中的发现相关。发现PFS与肿瘤内区域较低的免疫细胞浸润（CD3 +、CD4 +和CD11c +细胞）之间存在统计学上显著的正相关，并且肿瘤外区域免疫细胞数量增加与更长的PFS相关（CD3 +、CD4 +、CD8 +，均表达PD-1）。此外，一些免疫细胞亚群的分布与完全治疗反应相关（PD-1/PD-L1阳性CD4 +和PD-1阳性CD8 +细胞）。我们的结果表明，如果转移灶在肿瘤内特定免疫细胞亚型的分布较低，而在肿瘤外某些免疫细胞亚型的分布较高，则患者可能会有更好的ILP治疗结果。
