Expression of antigen processing and presenting molecules in brain metastasis of breast cancer.
Expression of antigen processing and presenting molecules in brain metastasis of breast cancer.
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DOI：
10.1007/s00262-011-1137-9
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发表时间：
2012-06
影响因子：
5.8
通讯作者：
Okada, Hideho
中科院分区：
文献类型：
--
作者：
Liu, Yan;Komohara, Yoshihiro;Domenick, Natalie;Ohno, Masasuke;Ikeura, Maki;Hamilton, Ronald L.;Horbinski, Craig;Wang, Xinhui;Ferrone, Soldano;Okada, Hideho
关键词：
人类白细胞抗原（HLA）I类抗原加工机制（APM）组分表达的缺陷可能对肿瘤的临床病程和对基于T细胞的免疫治疗的反应产生负面影响。由于乳腺癌脑转移的临床意义日益增加，APM成分的表达水平和CD 8 + T细胞浸润模式进行了分析，在原发性乳腺癌和转移性脑病变的乳腺癌免疫组化。未配对的50例原发性脑转移瘤和33例脑转移瘤的比较显示，脑病灶中β2-微球蛋白、抗原处理相关转运蛋白（TAP）1、TAP 2和钙连接蛋白的表达较低。尽管在15例配对病例中，原发性乳腺和脑病变之间的APM组分评分无显著差异，但与无已知脑转移的乳腺病变相比，最终发生脑转移的患者的原发性乳腺病变显示出较低的β2-微球蛋白、TAP 1和钙连接蛋白水平。无脑转移组CD 8 + T细胞浸润程度明显高于有脑转移组，且与TAP 1和Calnexin表达呈正相关。此外，小鼠肿瘤细胞稳定转染沉默发夹（sh）RNA的TAP 1表现出降低细胞毒性T淋巴细胞（CTL）在体外的易感性和增强自发性脑转移在体内。这些数据支持TAP 1在肿瘤细胞中表达的功能意义。总之，我们的数据表明，原发性乳腺癌中TAP 1或钙连接蛋白水平低或有缺陷的患者，由于T细胞免疫监视的缺陷，发生脑转移的风险可能更高。
Defects in human leukocyte antigen (HLA) class I antigen processing machinery (APM) component expression can have a negative impact on the clinical course of tumors and the response to T-cell-based immunotherapy. Since brain metastases of breast cancer are of increasing clinical significance, the APM component expression levels and CD8+ T-cell infiltration patterns were analyzed in primary breast and metastatic brain lesions of breast cancer by immunohistochemistry. Comparison of unpaired 50 primary and 33 brain metastases showed lower expression of β2-microgloblin, transporter associated with antigen processing (TAP) 1, TAP2 and calnexin in the brain lesions. Although no significant differences were found in APM component scores between primary breast and brain lesions in 15 paired cases, primary breast lesions of which patients eventually developed brain metastases showed lower levels of β2-microgloblin, TAP1 and calnexin compared with breast lesions without known brain metastases. The extent of CD8+ T cell infiltration was significantly higher in the lesions without metastasis compared with the ones with brain metastases, and was positively associated with the expression of TAP1 and calnexin. Furthermore, mouse tumor cells stably transfected with silencing hairpin (sh)RNA for TAP1 demonstrated a decreased susceptibility to cytotoxic T lymphocytes (CTL) in vitro and enhanced spontaneous brain metastasis in vivo. These data support the functional significance of TAP1 expression in tumor cells. Taken together, our data suggest that patients with low or defective TAP1 or calnexin in primary breast cancers may be at higher risks for developing brain metastasis due to the defects in T cell-based immunosurveillance.
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影响因子：
6.2
作者：
Gong, Yun;Han, Eric Yulong;Sneige, Nour
通讯作者：
Sneige, Nour
影响因子：
11.2
作者：
Herrmann, F;Lehr, HA;Seliger, B
通讯作者：
Seliger, B
影响因子：
15.9
作者：
MAIO, M;ALTOMONTE, M;FERRONE, S
通讯作者：
FERRONE, S
激素受体状态，肿瘤特征和预后：乳腺癌患者的前瞻性队列。
DOI：
10.1186/bcr1639
发表时间：
2007
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Dunnwald LK;Rossing MA;Li CI
通讯作者：
Li CI
影响因子：
3.8
作者：
Bauer, Katrina;Parise, Carol;Caggiano, Vincent
通讯作者：
Caggiano, Vincent