IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer.
IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer.
复制标题
淋巴细胞产生的γ-干扰素可诱导程序性死亡配体1（PD-L1）的表达，并促进卵巢癌进展。
DOI：
10.1038/bjc.2015.101
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发表时间：
2015-04-28
影响因子：
8.8
通讯作者：
Mandai, M.
中科院分区：
文献类型：
--
作者：
Abiko, K.;Matsumura, N.;Hamanishi, J.;Horikawa, N.;Murakami, R.;Yamaguchi, K.;Yoshioka, Y.;Baba, T.;Konishi, I.;Mandai, M.
肿瘤细胞上的PD-L1（程序性细胞死亡1配体1）通过与淋巴细胞上的受体PD-1结合抑制宿主免疫力，并促进卵巢癌小鼠模型中的腹膜播散。然而，PD-L1表达在卵巢癌微环境中如何调节仍不清楚。在卵巢癌临床样本中评估了CD 8阳性淋巴细胞的数量和肿瘤细胞中PD-L1的表达。评估了在改变IFN-γ信号的条件下小鼠模型中的PD-L1表达和肿瘤进展。在腹膜播散性肿瘤中，癌间质中的CD 8阳性细胞数量非常高，并且与肿瘤细胞上的PD-L1表达密切相关（P<0.001）。在小鼠模型中，去除IFNGR 1（干扰素-γ受体1）导致肿瘤细胞中PD-L1表达水平降低，肿瘤浸润CD 8阳性淋巴细胞数量增加，腹膜播散性肿瘤生长受到抑制，生存期延长（P=0.02）。皮下肿瘤注射IFN-γ诱导PD-L1表达并促进肿瘤生长，PD-L1耗竭完全消除了IFN-γ注射引起的肿瘤生长（P=0.01）。由CD 8阳性淋巴细胞分泌的干扰素-γ上调卵巢癌细胞上的PD-L1并促进肿瘤生长。淋巴细胞浸润和IFN-γ状态可能是卵巢癌抗PD-1或抗PD-L1治疗有效的关键。
PD-L1 (programmed cell death 1 ligand 1) on tumour cells suppresses host immunity through binding to its receptor PD-1 on lymphocytes, and promotes peritoneal dissemination in mouse models of ovarian cancer. However, how PD-L1 expression is regulated in ovarian cancer microenvironment remains unclear. The number of CD8-positive lymphocytes and PD-L1 expression in tumour cells was assessed in ovarian cancer clinical samples. PD-L1 expression and tumour progression in mouse models under conditions of altering IFN-γ signals was assessed. The number of CD8-positive cells in cancer stroma was very high in peritoneally disseminated tumours, and was strongly correlated to PD-L1 expression on the tumour cells (P<0.001). In mouse models, depleting IFNGR1 (interferon-γ receptor 1) resulted in lower level of PD-L1 expression in tumour cells, increased the number of tumour-infiltrating CD8-positive lymphocytes, inhibition of peritoneal disseminated tumour growth and longer survival (P=0.02). The injection of IFN-γ into subcutaneous tumours induced PD-L1 expression and promoted tumour growth, and PD-L1 depletion completely abrogated tumour growth caused by IFN-γ injection (P=0.01). Interferon-γ secreted by CD8-positive lymphocytes upregulates PD-L1 on ovarian cancer cells and promotes tumour growth. The lymphocyte infiltration and the IFN-γ status may be the key to effective anti-PD-1 or anti-PD-L1 therapy in ovarian cancer.
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DOI：
10.1038/nrclinonc.2013.5
发表时间：
2013-04
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
通讯作者：
--
影响因子：
11.2
作者：
Blank, C;Brown, I;Gajewski, TF
通讯作者：
Gajewski, TF
影响因子：
4.4
作者：
Indraccolo, Stefano;Pfeffer, Ulrich;Amadori, Alberto
通讯作者：
Amadori, Alberto
DOI：
10.1073/pnas.192461099
发表时间：
2002-09-17
影响因子：
11.1
作者：
Iwai, Y;Ishida, M;Minato, N
通讯作者：
Minato, N
影响因子：
5.2
作者：
Hamanishi, Junzo;Mandai, Masaki;Konishi, Ikuo
通讯作者：
Konishi, Ikuo