Vuylsteke Ronald J C L M, Molenkamp Barbara G, Gietema Hester A, van Leeuwen Paul A M, Wijnands Pepijn G J T B, Vos Wim, van Diest Paul J, Scheper Rik J, Meijer Sybren, de Gruijl Tanja D
Department of Surgical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
Cancer Res. 2004 Nov 15;64(22):8456-60. doi: 10.1158/0008-5472.CAN-03-3251.
The initial tumor-draining lymph node, the sentinel lymph node, not only constitutes the first expected site of micrometastasis but also the first point of contact between tumor-associated antigens and the adaptive immune system. A tumor-induced decrease in the frequency and activation state of sentinel lymph node dendritic cells will impair the generation of effective antitumor T-cell responses and increase the likelihood of metastatic spread. Here, we demonstrate that intradermal administration of granulocyte macrophage-colony stimulating factor around the excision site of stage I primary melanoma tumors increases the number and activation state of dendritic cells in the paracortical areas of the sentinel lymph node and enhances their binding to T cells. We conclude that local treatment of melanoma patients with granulocyte macrophage-colony stimulating factor, before surgery, conditions the sentinel lymph node microenvironment to enhance mature dendritic cell recruitment and hypothesize that this may be more conducive to the generation of T-cell-mediated antitumor immunity.
初始引流肿瘤的淋巴结，即前哨淋巴结，不仅是微转移的首个预期部位，也是肿瘤相关抗原与适应性免疫系统的首个接触点。肿瘤诱导的前哨淋巴结树突状细胞频率和激活状态降低会损害有效的抗肿瘤T细胞反应的产生，并增加转移扩散的可能性。在此，我们证明在I期原发性黑色素瘤肿瘤切除部位周围皮内注射粒细胞巨噬细胞集落刺激因子可增加前哨淋巴结副皮质区树突状细胞的数量和激活状态，并增强它们与T细胞的结合。我们得出结论，术前用粒细胞巨噬细胞集落刺激因子对黑色素瘤患者进行局部治疗可调节前哨淋巴结微环境，以增强成熟树突状细胞的募集，并推测这可能更有利于产生T细胞介导的抗肿瘤免疫。
