Immunomodulation by imiquimod in patients with high-risk primary melanoma.
Immunomodulation by imiquimod in patients with high-risk primary melanoma.
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DOI：
10.1038/jid.2011.247
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发表时间：
2012-01
影响因子：
6.5
通讯作者：
Craft, Noah
中科院分区：
文献类型：
--
作者：
Narayan, Rupa;Nguyen, Hong;Bentow, Jason J.;Moy, Lauren;Lee, Diana K.;Greger, Stephanie;Haskell, Jacquelyn;Vanchinathan, Veena;Chang, Pei-Lin;Tsui, Shanli;Konishi, Tamiko;Comin-Anduix, Begonya;Dauphine, Christine;Vargas, Hernan I.;Economou, James S.;Ribas, Antoni;Bruhn, Kevin W.;Craft, Noah
咪喹莫特是一种合成的Toll样受体7(TLR7)激动剂，被批准用于局部治疗光化性角化病、浅表性基底细胞癌和生殖器疣。咪喹莫特治疗恶性雀斑狼疮的治愈率为80%-100%，但缺乏对侵袭性黑色素瘤的研究。我们进行了一项初步研究，以确定咪喹莫特在高危黑色素瘤患者中诱导的局部、区域和全身免疫反应的特征。在用安慰剂或咪喹莫特乳膏治疗原发黑色素瘤活检部位后，我们测量了治疗后皮肤、前哨淋巴结(SLN)和外周血液中的免疫反应。用5%咪喹莫特乳膏治疗原发性黑色素瘤时，皮肤中的CD4+和CD8+T细胞以及SLN中的CD4+T细胞均增加。皮肤中的CD8+T细胞多为CD25阴性。我们没有检测到外周血中CD8+T细胞的任何增加，这些T细胞识别人类白细胞抗原-A*0201限制的黑色素瘤表位。这项小型先导性研究的结果表明，外用咪喹莫特治疗可以增加皮肤和SLN中局部和局部T细胞的数量。有必要进一步研究TLR7免疫调节通路，作为结合手术进行有效的黑色素瘤免疫治疗的基础。
Imiquimod is a synthetic Toll-like receptor 7 (TLR7) agonist approved for the topical treatment of actinic keratoses, superficial basal cell carcinoma, and genital warts. Imiquimod leads to an 80–100% cure rate of lentigo maligna, but studies of invasive melanoma are lacking. We conducted a pilot study to characterize the local, regional, and systemic immune responses induced by imiquimod in patients with high-risk melanoma. After treatment of the primary melanoma biopsy site with placebo or imiquimod cream, we measured immune responses in the treated skin, sentinel lymph nodes (SLN), and peripheral blood. Treatment of primary melanomas with 5% imiquimod cream was associated with an increase in both CD4+ and CD8+ T cells in the skin, and CD4+ T cells in the SLN. Most of the CD8+ T cells in the skin were CD25 negative. We could not detect any increases in CD8+ T cells specifically recognizing HLA-A*0201-restricted melanoma epitopes in the peripheral blood. The findings from this small pilot study demonstrate that topical imiquimod treatment results in enhanced local and regional T cell numbers in both the skin and SLN. Further research into TLR7 immunomodulating pathways as a basis for effective immunotherapy against melanoma in conjunction with surgery is warranted.
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影响因子：
9.2
作者：
Shu, Suyu;Cochran, Alistair J.;Maecker, Holden T.
通讯作者：
Maecker, Holden T.
影响因子：
7.4
作者：
Torres A;Storey L;Anders M;Miller RL;Bulbulian BJ;Jin J;Raghavan S;Lee J;Slade HB;Birmachu W
通讯作者：
Birmachu W
影响因子：
10.3
作者：
Ooi, T;Barnetson, RS;Halliday, GM
通讯作者：
Halliday, GM
影响因子：
11.5
作者：
Comin-Anduix, B;Gualberto, A;Ribas, A
通讯作者：
Ribas, A
影响因子：
3.6
作者：
De Giorgi, Vincenzo;Salvini, Camilla;Massi, Daniela
通讯作者：
Massi, Daniela