Maes Wim, Verschuere Tina, Van Hoylandt Anaïs, Boon Louis, Van Gool Stefaan
Laboratory for Thrombosis Research, Interdisciplinary Research Facility Life Sciences Kulak, E. Sabbelaan 53, 8500 Kortrijk, Belgium.
Clin Dev Immunol. 2013;2013:952469. doi: 10.1155/2013/952469. Epub 2013 Apr 23.
The recruitment and activation of regulatory T cells (Tregs) in the micro-environment of malignant brain tumors has detrimental effects on antitumoral immune responses. Hence, local elimination of Tregs within the tumor micro-environment represents a highly valuable tool from both a fundamental and clinical perspective. In the syngeneic experimental GL261 murine glioma model, Tregs were prophylactically eliminated through treatment with PC61, an anti-CD25 mAb. This resulted in specific elimination of CD4+CD25hiFoxp3+ Treg within brain-infiltrating lymphocytes and complete protection against subsequent orthotopic GL261 tumor challenge. Interestingly, PC61-treated mice also showed a pronounced infiltration of CD11b+ myeloid cells in the brain. Phenotypically, these cells could not be considered as Gr-1+ myeloid-derived suppressor cells (MDSC) but were identified as F4/80+ macrophages and granulocytes.
恶性脑肿瘤微环境中调节性T细胞(Tregs)的募集和激活对抗肿瘤免疫反应具有有害影响。因此,从基础和临床角度来看,在肿瘤微环境中局部清除Tregs是一种非常有价值的手段。在同基因实验性GL261小鼠胶质瘤模型中,通过用抗CD25单克隆抗体PC61进行治疗,预防性地清除了Tregs。这导致脑浸润淋巴细胞内CD4 + CD25hiFoxp3 + Treg的特异性清除,并对随后的原位GL261肿瘤攻击提供了完全保护。有趣的是,用PC61治疗的小鼠在脑中还显示出CD11b +髓样细胞的明显浸润。从表型上看,这些细胞不能被认为是Gr-1 +髓样来源的抑制细胞(MDSC),而是被鉴定为F4/80 +巨噬细胞和粒细胞。