Prognostic and predictive value of PDL1 expression in breast cancer.
Prognostic and predictive value of PDL1 expression in breast cancer.
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DOI：
10.18632/oncotarget.3216
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发表时间：
2015-03-10
期刊：
影响因子：
--
通讯作者：
Bertucci F
中科院分区：
文献类型：
--
作者：
Sabatier R;Finetti P;Mamessier E;Adelaide J;Chaffanet M;Ali HR;Viens P;Caldas C;Birnbaum D;Bertucci F
程序性细胞死亡受体配体1(PDL1)在乳腺癌中的表达研究较少。近年来，PD1/PDL1抑制剂在不同肿瘤中显示出良好的疗效，PDL1在肿瘤中的表达与其治疗反应之间存在相关性。我们回顾分析了45个乳腺癌细胞系和5,454个乳腺癌组织中PDL1mRNA的表达。与正常乳腺标本相比，PDL1在20%的临床标本和38%的基底肿瘤中表达上调。高表达与预后不良有关(肿瘤体积大、分级高、ER阴性、PR阴性、ERBB2阳性、高增殖、基底和ERBB2富集型)。PDL1表达上调与强烈细胞毒性局部免疫反应的生物学征象有关。PDL1表达上调与整个人群的生存率无关，但与基底肿瘤中较好的无转移和总体特定生存率相关，与临床病理特征无关。PDL1表达上调的患者新辅助化疗后病理完全缓解率较高(50%比21%)。总而言之，PDL1上调在基底乳腺癌中更为常见，与T细胞细胞毒性免疫反应增强有关。在这种侵袭性亚型中，上调与更好的生存和对化疗的反应有关。用PDL1抑制剂重新激活处于休眠状态的肿瘤浸润性淋巴细胞可能是治疗PDL1上调的基础乳腺癌的有希望的策略。
Expression of programmed cell death receptor ligand 1 (PDL1) has been scarcely studied in breast cancer. Recently PD1/PDL1-inhibitors have shown promising results in different carcinomas with correlation between PDL1 tumor expression and responses. We retrospectively analyzed PDL1 mRNA expression in 45 breast cancer cell lines and 5,454 breast cancers profiled using DNA microarrays. Compared to normal breast samples, PDL1 expression was upregulated in 20% of clinical samples and 38% of basal tumors. High expression was associated with poor-prognosis features (large tumor size, high grade, ER-negative, PR-negative, ERBB2-positive status, high proliferation, basal and ERBB2-enriched subtypes). PDL1 upregulation was associated with biological signs of strong cytotoxic local immune response. PDL1 upregulation was not associated with survival in the whole population, but was associated with better metastasis-free and overall specific survivals in basal tumors, independently of clinicopathological features. Pathological complete response after neoadjuvant chemotherapy was higher in case of PDL1 upregulation (50% versus 21%). In conclusion, PDL1 upregulation, more frequent in basal breast cancers, was associated with increased T-cell cytotoxic immune response. In this aggressive subtype, upregulation was associated with better survival and response to chemotherapy. Reactivation of dormant tumor-infiltrating lymphocytes by PDL1-inhibitors could represent promising strategy in PDL1-upregulated basal breast cancer.
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影响因子：
64.8
作者：
Ellis, Matthew J.;Ding, Li;Shen, Dong;Luo, Jingqin;Suman, Vera J.;Wallis, John W.;Van Tine, Brian A.;Hoog, Jeremy;Goiffon, Reece J.;Goldstein, Theodore C.;Ng, Sam;Lin, Li;Crowder, Robert;Snider, Jacqueline;Ballman, Karla;Weber, Jason;Chen, Ken;Koboldt, Daniel C.;Kandoth, Cyriac;Schierding, William S.;McMichael, Joshua F.;Miller, Christopher A.;Lu, Charles;Harris, Christopher C.;McLellan, Michael D.;Wendl, Michael C.;DeSchryver, Katherine;Allred, D. Craig;Esserman, Laura;Unzeitig, Gary;Margenthaler, Julie;Babiera, G. V.;Marcom, P. Kelly;Guenther, J. M.;Leitch, Marilyn;Hunt, Kelly;Olson, John;Tao, Yu;Maher, Christopher A.;Fulton, Lucinda L.;Fulton, Robert S.;Harrison, Michelle;Oberkfell, Ben;Du, Feiyu;Demeter, Ryan;Vickery, Tammi L.;Elhammali, Adnan;Piwnica-Worms, Helen;McDonald, Sandra;Watson, Mark;Dooling, David J.;Ota, David;Chang, Li-Wei;Bose, Ron;Ley, Timothy J.;Piwnica-Worms, David;Stuart, Joshua M.;Wilson, Richard K.;Mardis, Elaine R.
通讯作者：
Mardis, Elaine R.
DOI：
10.1073/pnas.0912708107
发表时间：
2010-04-13
影响因子：
11.1
作者：
Gatza, Michael L.;Lucas, Joseph E.;Nevins, Joseph R.
通讯作者：
Nevins, Joseph R.
影响因子：
8.4
作者：
Droeser, Raoul A.;Hirt, Christian;Tornillo, Luigi
通讯作者：
Tornillo, Luigi
影响因子：
45.3
作者：
Bianchini, Giampaolo;Qi, Yuan;Pusztai, Lajos
通讯作者：
Pusztai, Lajos
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel