van der Bruggen P
Ludwig Institute for Cancer Research.
Bull Mem Acad R Med Belg. 2009;164(5-6):183-91; discussion 192.
Human tumor metastases are often infiltrated by T lymphocytes that are specific for tumor antigens, but these metastases progress anyway. The spontaneous anti-tumor immune response seems thus to become ineffective, probably because the effector T cells become anergic. This anergy could result from inhibitory mechanisms orchestrated by the tumor cells. We have observed that recently stimulated human cytolytic T cell clones lose transiently their capacity to secrete cytokines. This anergy is correlated with the absence of colocalization of the T cell receptors (TCR) and the CD8 co-receptors. Effector functions' and TCR/CD8 colocalization are recovered by treating cells with galectin-3 ligands, suggesting that exracellular galectin-3 forms glycoprotein-galectin lattices, which decrease the TCR mobility on the surface of anergic T lymphocytes. Galectin-3 is frequently released by tumor cells. This new mechanism of anergy could thus also explain the loss of functions of the tumor-infiltrating lymphocytes, because these lymphocytes recover their effector functions and TCR/CD8 colocalization after ex vivo treatment with galectin-3 ligands. These results could lead to new therapeutical strategies.
人类肿瘤转移灶常被肿瘤抗原特异性T淋巴细胞浸润，但这些转移灶仍会进展。因此，自发的抗肿瘤免疫反应似乎变得无效，这可能是因为效应T细胞变得无反应性。这种无反应性可能源于肿瘤细胞精心策划的抑制机制。我们观察到，最近受到刺激的人类细胞毒性T细胞克隆会暂时失去分泌细胞因子的能力。这种无反应性与T细胞受体（TCR）和CD8共受体的共定位缺失有关。通过用半乳糖凝集素-3配体处理细胞可恢复效应功能和TCR/CD8共定位，这表明细胞外半乳糖凝集素-3形成糖蛋白-半乳糖凝集素晶格，从而降低无反应性T淋巴细胞表面TCR的流动性。肿瘤细胞经常释放半乳糖凝集素-3。因此，这种新的无反应性机制也可以解释肿瘤浸润淋巴细胞功能的丧失，因为这些淋巴细胞在用半乳糖凝集素-3配体进行体外处理后可恢复其效应功能和TCR/CD8共定位。这些结果可能会带来新的治疗策略。
