Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape.
Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape.
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DOI：
10.1126/scitranslmed.3003689
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发表时间：
2012-03-28
影响因子：
17.1
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Taube JM;Anders RA;Young GD;Xu H;Sharma R;McMiller TL;Chen S;Klein AP;Pardoll DM;Topalian SL;Chen L
虽然许多人类癌症如黑色素瘤表达T细胞识别的肿瘤抗原，但宿主免疫反应通常无法控制肿瘤生长，原因尚不清楚。在这里，我们发现黑素细胞表达B7-H1（PD-L1）（一种免疫抑制分子）与人类黑素细胞病变中肿瘤浸润淋巴细胞（TIL）的存在之间存在强烈的相关性：98%的B7-H1+肿瘤与TIL相关，而B7-H1−肿瘤仅为28%。事实上，B7-H1+黑素细胞几乎总是定位于紧邻TIL。B7-H1/TIL共定位不仅在黑色素瘤中，而且在发炎的良性痣中，表明B7-H1表达可能代表宿主对组织炎症的反应。干扰素-γ是B7-H1表达的主要诱导物，在B7-H1+肿瘤和TIL的界面处检测到，而在B7-H1−肿瘤中未发现。因此，TIL实际上可能通过分泌驱动肿瘤B7-H1表达的细胞因子来触发其自身的抑制。与这一假设一致，B7-H1+转移性黑色素瘤患者的总生存期比B7-H1−转移性黑色素瘤患者显著延长。因此，B7-H1/PD-1通路的诱导可能代表肿瘤细胞响应内源性抗肿瘤活性而产生的适应性免疫抵抗机制，并可能解释黑色素瘤如何在内源性抗肿瘤免疫应答的情况下逃避免疫破坏。这些观察结果表明，阻断该途径的疗法可能使B7-H1+肿瘤患者受益。
Although many human cancers such as melanoma express tumor antigens recognized by T cells, host immune responses often fail to control tumor growth for as yet unexplained reasons. Here, we found a strong association between melanocyte expression of B7-H1 (PD-L1), an immune-inhibitory molecule, and the presence of tumor-infiltrating lymphocytes (TILs) in human melanocytic lesions: 98% of B7-H1+ tumors were associated with TILs compared with only 28% of B7-H1− tumors. Indeed, B7-H1+ melanocytes were almost always localized immediately adjacent to TILs. B7-H1/TIL colocalization was identified not only in melanomas but also in inflamed benign nevi, indicating that B7-H1 expression may represent a host response to tissue inflammation. Interferon-γ, a primary inducer of B7-H1 expression, was detected at the interface of B7-H1+ tumors and TILs, whereas none was found in B7-H1− tumors. Therefore, TILs may actually trigger their own inhibition by secreting cytokines that drive tumor B7-H1 expression. Consistent with this hypothesis, overall survival of patients with B7-H1+ metastatic melanoma was significantly prolonged compared with that of patients with B7-H1− metastatic melanoma. Therefore, induction of the B7-H1/PD-1 pathway may represent an adaptive immune resistance mechanism exerted by tumor cells in response to endogenous antitumor activity and may explain how melanomas escape immune destruction despite endogenous antitumor immune responses. These observations suggest that therapies that block this pathway may benefit patients with B7-H1+ tumors.
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影响因子：
32.4
作者：
Dong, HD;Zhu, GF;Chen, LP
通讯作者：
Chen, LP
DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
45.3
作者：
Balch, Charles M.;Gershenwald, Jeffrey E.;Sondak, Vernon K.
通讯作者：
Sondak, Vernon K.
影响因子：
32.4
作者：
Butte, Manish J.;Keir, Mary E.;Freeman, Gordon J.
通讯作者：
Freeman, Gordon J.
影响因子：
2.9
作者：
Fukunaga, A;Miyamoto, M;Katoh, H
通讯作者：
Katoh, H