Na Il-Kang, Keilholz Ulrich, Letsch Anne, Bauer Sandra, Asemissen Anne Marie, Nagorsen Dirk, Thiel Eckhard, Scheibenbogen Carmen
Department of Hematology, Oncology and Transfusion Medicine, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.
Cancer Immunol Immunother. 2007 Mar;56(3):391-6. doi: 10.1007/s00262-006-0198-7. Epub 2006 Jul 19.
T-cell trafficking is determined by expression patterns of chemokine receptors. The chemokine receptor CXCR3 is expressed on a subpopulation of type 1 T cells and plays an important role for migration of T cells into inflamed and tumor tissues. Here, we studied the chemokine receptor expression on specific T cells generated against the neoantigen keyhole limpet hemocyanin (KLH) in patients who had been immunized in the context of a tumor peptide vaccination trial with or without the adjuvant granulocyte-macrophage colony-stimulating factor (GM-CSF). In patients immunized in the presence of GM-CSF the fraction of CXCR3(+) KLH-specific T cells was significantly higher than in patients immunized in the absence of GM-CSF (median 45 vs. 20%, P = 0.001). In contrast, the chemokine receptor CCR4, associated with migration to the skin was found in both cohorts on less than 10% of KLH-specific T cells. These results show that CXCR3 expression on vaccine-induced T cells can be modulated by modifying the local vaccine milieu.
T细胞迁移由趋化因子受体的表达模式决定。趋化因子受体CXCR3在1型T细胞亚群上表达,对T细胞迁移至炎症组织和肿瘤组织起着重要作用。在此,我们研究了在肿瘤肽疫苗接种试验中接种或未接种佐剂粒细胞巨噬细胞集落刺激因子(GM-CSF)的患者体内,针对新抗原钥孔戚血蓝蛋白(KLH)产生的特异性T细胞上趋化因子受体的表达情况。在有GM-CSF存在的情况下接种疫苗的患者中,CXCR3(+) KLH特异性T细胞的比例显著高于无GM-CSF情况下接种疫苗的患者(中位数分别为45%和2()%,P = 0.001)。相反,在两个队列中,与迁移至皮肤相关的趋化因子受体CCR4在不到10%的KLH特异性T细胞中被发现。这些结果表明,通过改变局部疫苗环境可以调节疫苗诱导的T细胞上CXCR3的表达。