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首页> 外文期刊>Clinical and experimental metastasis >CD4(+)FOXP3(+) T regulatory cells decrease and CD3(+)CD8(+) T cells recruitment in TILs from melanoma metastases after electrochemotherapy
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CD4(+)FOXP3(+) T regulatory cells decrease and CD3(+)CD8(+) T cells recruitment in TILs from melanoma metastases after electrochemotherapy

机译：CD4（+）FOXP3（+）T调节细胞减少，电化学疗法后黑色素瘤转移的TIL中的CD3（+）CD8（+）T细胞募集

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Electrochemotherapy (ECT) represents an effective local treatment for skin unresectable melanoma metastases with high overall objective response rate. ECT is based on the combination of anti-neoplastic drugs administration and cancer cells electroporation. Whether ECT can also activate the immune system is a matter of debate, however a significant recruitment of dendritic cells in melanoma treated metastases has been described. Herein we investigated immediate and late effects of ECT treatment on T cell subsets in ECT-treated lesions by fluorescent immunohistochemistry. Biopsies from melanoma patients (n = 10) were taken before ECT (t0), at d1 and d14 from treatment. At t0, CD3(+)CD4(+) T cells were the most represented T cells, well detected in the perilesional dermis, particularly at tumour margin, while CD3(+)CD8(+) T cells were less represented. CD4(+)FOXP3(+) T regulatory (Treg) cells were present in the perilesional dermis and within the lesion. ECT induced a significant decrease of CD4(+)FOXP3(+) Treg cells percentage in the perilesional dermis, observed at d1 and at d14 (p < 0.001). CD3(+)CD8(+) T cells frequency significantly increased at d14 from treatment in the perilesional dermis (p < 0.001). Furthermore calreticulin translocation to the plasma membrane, a hallmark of immunogenic cell death, was observed in metastatic cells after ECT. The data reported here confirm that ECT induces a local response, with a lymphoid infiltrate characterized by CD4(+)FOXP3(+) Treg cells decrease and CD3(+)CD8(+) T cells recruitment in the treated lesions. These results might contribute to design novel combinational therapeutic approaches with ECT and immunotherapy in order to generate a systemic long-lasting anti-melanoma immunity.
机译：电化学疗法（ECT）代表了不可切除的黑色素瘤皮肤转移的有效局部治疗，具有较高的总体客观反应率。 ECT基于抗肿瘤药物的给药和癌细胞的电穿孔相结合。 ECT是否还可以激活免疫系统尚有争议，但是已经描述了在黑色素瘤治疗的转移灶中树突状细胞的大量募集。本文中，我们通过荧光免疫组织化学研究了ECT治疗对ECT治疗病变中T细胞亚群的即时和晚期效应。黑色素瘤患者的活检（n = 10）是在治疗前d1和d14在ECT（t0）之前进行的。在t0时，CD3（+）CD4（+）T细胞是最典型的T细胞，在病灶周围的真皮中，尤其是在肿瘤边缘，可以很好地检测到，而CD3（+）CD8（+）T细胞的代表性较低。 CD4（+）FOXP3（+）T调节（Treg）细胞存在于病灶周围的真皮中和病灶内。在d1和d14观察到，ECT诱导了病灶周围真皮中CD4（+）FOXP3（+）Treg细胞百分比的显着降低（p <0.001）。 CD3（+）CD8（+）T细胞的频率在病灶周皮治疗后第14天显着增加（p <0.001）。此外，在ECT后转移细胞中观察到钙网蛋白易位至质膜，这是免疫原性细胞死亡的标志。此处报道的数据证实ECT诱导局部反应，其特征是CD4（+）FOXP3（+）Treg细胞减少，淋巴样浸润减少，而CD3（+）CD8（+）T细胞募集。这些结果可能有助于设计与ECT和免疫疗法结合的新型治疗方法，以产生全身性持久的抗黑素瘤免疫力。

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