Perdicchio Maurizio, Cornelissen Lenneke A M, Streng-Ouwehand Ingeborg, Engels Steef, Verstege Marleen I, Boon Louis, Geerts Dirk, van Kooyk Yvette, Unger Wendy W J
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Oncotarget. 2016 Feb 23;7(8):8771-82. doi: 10.18632/oncotarget.6822.
The increased presence of sialylated glycans on the tumor surface has been linked to poor prognosis, yet the effects on tumor-specific T cell immunity are hardly studied. We here show that hypersialylation of B16 melanoma substantially influences tumor growth by preventing the formation of effector T cells and facilitating the presence of high regulatory T cell (Treg) frequencies. Knock-down of the sialic acid transporter created "sialic acid low" tumors, that grew slower in-vivo than hypersialylated tumors, altered the Treg/Teffector balance, favoring immunological tumor control. The enhanced effector T cell response in developing "sialic acid low" tumors was preceded by and dependent on an increased influx and activity of Natural Killer (NK) cells. Thus, tumor hypersialylation orchestrates immune escape at the level of NK and Teff/Treg balance within the tumor microenvironment, herewith dampening tumor-specific T cell control. Reducing sialylation provides a therapeutic option to render tumors permissive to immune attack.
肿瘤表面唾液酸化聚糖的增多与预后不良有关，但对肿瘤特异性T细胞免疫的影响却鲜有研究。我们在此表明，B16黑色素瘤的高唾液酸化通过阻止效应T细胞的形成和促进高调节性T细胞（Treg）频率的存在，极大地影响肿瘤生长。敲低唾液酸转运体产生了“低唾液酸”肿瘤，其在体内生长比高唾液酸化肿瘤更慢，改变了Treg/效应T细胞平衡，有利于免疫性肿瘤控制。在发育中的“低唾液酸”肿瘤中，效应T细胞反应增强之前并依赖于自然杀伤（NK）细胞流入和活性的增加。因此，肿瘤高唾液酸化在肿瘤微环境中的NK和Teff/Treg平衡水平上精心策划免疫逃逸，从而削弱肿瘤特异性T细胞控制。减少唾液酸化提供了一种使肿瘤易于受到免疫攻击的治疗选择。
