Blockade of programmed death ligand 1 enhances the therapeutic efficacy of combination immunotherapy against melanoma.
Blockade of programmed death ligand 1 enhances the therapeutic efficacy of combination immunotherapy against melanoma.
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DOI：
10.4049/jimmunol.0904114
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发表时间：
2010-04-01
期刊：
影响因子：
--
通讯作者：
Mulé JJ
中科院分区：
文献类型：
--
作者：
Pilon-Thomas S;Mackay A;Vohra N;Mulé JJ
抗肿瘤 T 细胞反应的抑制可以通过 T 细胞上的程序性死亡 1 (PD-1) 受体与其配体 PD-L1 之间的有效相互作用介导。 PD-L1 在小鼠骨髓源性树突状细胞 (DC) 和 B16 黑色素瘤中高表达。在这项研究中，体外阻断 DC 上的 PD-L1 相互作用导致抗原特异性 T 细胞增强 IFN-γ 的产生和细胞毒性。在体内，抗PD-L1抗体加上黑色素瘤肽脉冲DC的全身给药导致黑色素瘤肽特异性CD8+T细胞数量增加，但这种组合不足以延缓已形成的B16黑色素瘤的生长。虽然添加 600 拉德的全身照射 (TBI) 延迟了肿瘤生长，但需要进一步过继转移抗原特异性 CD8+ T 细胞以实现肿瘤消退和治疗小鼠的长期存活。用抗 PD-L1 抗体治疗的淋巴细胞减少小鼠表现出过继转移 T 细胞的激活和持久性增加，包括浸润肿瘤块的更多 CD8+ T 细胞。总之，这些研究支持阻断 PD-L1 信号传导作为增强针对黑色素瘤的联合免疫治疗方法的一种手段。
Inhibition of anti-tumor T cell responses can be mediated by the productive interaction between the programmed death-1 (PD-1) receptor on T cells and its ligand PD-L1. PD-L1 is highly expressed on both murine bone marrow-derived dendritic cells (DC) and B16 melanoma. In this study, in vitro blockade of PD-L1 interaction on DC led to enhanced IFN-gamma production and cytotoxicity by antigen-specific T cells. In vivo, the systemic administration of anti-PD-L1 antibody plus melanoma peptide-pulsed DC resulted in a higher number of melanoma peptide-specific CD8+ T cells but this combination was insufficient to delay the growth of established B16 melanoma. While the addition of 600 rad of total body irradiation (TBI) delayed tumor growth, further adoptive transfer of antigen-specific CD8+ T cells was needed to achieve tumor regression and long-term survival of the treated mice. Lymphopenic mice treated with anti-PD-L1 antibody demonstrated increased activation and persistence of adoptively transferred T cells, including a higher number of CD8+ T cells infiltrating the tumor mass. Together, these studies support the blocking of PD-L1 signaling as a means to enhance combined immunotherapy approaches against melanoma.
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影响因子：
32.4
作者：
Ernst, B;Lee, DS;Surh, CD
通讯作者：
Surh, CD
通过淋巴结消除来清除稳态细胞因子下沉，增强了采用转移的肿瘤特异性CD8+ T细胞的功效。
影响因子：
15.3
作者：
Gattinoni, Luca;Finkelstein, Steven E;Klebanoff, Christopher A;Antony, Paul A;Palmer, Douglas C;Spiess, Paul J;Hwang, Leroy N;Yu, Zhiya;Wrzesinski, Claudia;Heimann, David M;Surh, Charles D;Rosenberg, Steven A;Restifo, Nicholas P
通讯作者：
Restifo, Nicholas P
影响因子：
4.4
作者：
Keir, Mary E.;Freeman, Gordon J.;Sharpe, Arlene H.
通讯作者：
Sharpe, Arlene H.
影响因子：
11.5
作者：
Nomi, Takeo;Sho, Masayuki;Nakajima, Yoshiyuki
通讯作者：
Nakajima, Yoshiyuki
影响因子：
82.9
作者：
Nestle, FO;Alijagic, S;Schadendorf, D
通讯作者：
Schadendorf, D