转移性黑色素瘤患者皮内注射粒细胞-巨噬细胞集落刺激因子(GM-CSF)可招募树突状细胞。

M L Nasi, P Lieberman, K J Busam, V Prieto, K S Panageas, J J Lewis, A N Houghton, P B Chapman
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摘要

树突状细胞(dc)是皮肤中主要的抗原呈递细胞。我们假设皮内注射粒细胞-巨噬细胞集落刺激因子(GM-CSF)会将dc招募到黑色素瘤皮肤转移处,并增强自体黑色素瘤抗原向宿主T细胞的呈递。16例皮肤或皮下黑色素瘤转移患者接受GM-CSF连续10天注射,分别注射到单个真皮转移灶和正常皮肤部位,注射剂量分为4种(10、20、40或80微克/次)。对治疗前后的皮肤和肿瘤活检组织进行t细胞、b细胞、巨噬细胞和DC免疫组织化学标记物染色。阳性细胞采用盲法定量。注射GM-CSF后,皮肤和肿瘤中dc (HLA-DR+、S100+、XIIIa因子+)和CD45R0+ T细胞数量均显著增加。未注射对照肿瘤显示HLA-DR+细胞或t细胞浸润未增加,但S100+和因子XIIIa+细胞增加,提示非dc群体。以这种方式给药的ID GM-CSF将dc招募到黑色素瘤肿瘤和正常皮肤中。虽然没有观察到抗肿瘤作用,但这代表了一种为疫苗递送准备皮肤部位的潜在方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Intradermal injection of granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with metastatic melanoma recruits dendritic cells.

Dendritic cells (DCs) are the main antigen-presenting cells in the skin. We hypothesized that intradermal (i.d.) injection of granulocyte-macrophage colony-stimulating factor (GM-CSF) would recruit DCs into melanoma skin metastases and enhance autologous melanoma antigen presentation to host T cells. Sixteen patients with cutaneous or subcutaneous melanoma metastases were treated with GM-CSF injected i.d. into a single dermal metastasis and into a normal skin site for 10 consecutive days at one of four dose levels (10, 20, 40, or 80 microg/injection). Pretreatment and post-treatment skin and tumor biopsies were stained for a panel of T-cell, B-cell, macrophage, and DC immunohistochemical markers. Positive cells were quantitated in a blinded fashion. There was a significant increase in the number of DCs (HLA-DR+, S100+, factor XIIIa+) and CD45R0+ T cells in the skin and in the tumors Injected with GM-CSF at all dose levels. Uninjected control tumors showed no increase in HLA-DR+ cells or T-cell infiltrate, but did show an Increase in S100+ and factor XIIIa+ cells, suggesting a non-DC population. ID GM-CSF administered in this manner recruited DCs into melanoma tumors and normal skin. Although no antitumor effects were seen, this represents a potential method of preparing skin sites for vaccine delivery.

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