Profiling the Tumour Immune Microenvironment in Pancreatic Neuroendocrine Neoplasms with Multispectral Imaging Indicates Distinct Subpopulation Characteristics Concordant with WHO 2017 Classification.
Profiling the Tumour Immune Microenvironment in Pancreatic Neuroendocrine Neoplasms with Multispectral Imaging Indicates Distinct Subpopulation Characteristics Concordant with WHO 2017 Classification.
复制标题
DOI：
10.1038/s41598-018-31383-9
复制
发表时间：
2018-09-03
影响因子：
4.6
通讯作者：
Nagino M
中科院分区：
文献类型：
--
作者：
Takahashi D;Kojima M;Suzuki T;Sugimoto M;Kobayashi S;Takahashi S;Konishi M;Gotohda N;Ikeda M;Nakatsura T;Ochiai A;Nagino M
我们成功地确定了pNENs和胰腺导管腺癌（PDAC）之间的免疫微环境的差异，并使用多光谱荧光成像系统pNENs之间的组织学依赖的变异性。研究了包括52个pNEN和18个PDAC的肿瘤组织样品。对pNENs中的肿瘤浸润淋巴细胞（TIL）及其PD-1和PD-L1表达进行全面定量分析，并随后与PDAC中的TIL及其PD-1和PD-L1表达进行比较。主成分分析显示，组织免疫特征与肿瘤组织学相关，NET、NEC和PDAC观察到不同的组。虽然NEC和一些PDAC具有含有丰富TIL的热免疫微环境，但NET具有含有少量TIL的冷免疫微环境。此外，在NETs中，上皮内PD-1high T细胞和PD-L1high II型巨噬细胞的数量根据分级而升高。单因素分析显示，淋巴结转移、分级、分期、PD-1high T细胞和PD-L1high II型巨噬细胞是无复发生存期（RFS）的预测因子，而分级和PD-1high T细胞是总生存期（OS）的预后因子。我们还发现PD-1high T细胞和PD-L1high II型巨噬细胞与pNEN的预后不良相关。我们的研究结果支持WHO 2017年肿瘤分类标准，该标准区分了G3 NET和NEC。
We successfully determined the difference of immune microenvironments between pNENs and pancreatic ductal adenocarcinomas (PDACs), and the histology-dependent variability among pNENs using multispectral fluorescent imaging system. Tumour tissue samples including 52 pNENs and 18 PDACs were investigated. The tumour-infiltrating lymphocytes (TILs), their PD-1 and PD-L1 expression in the pNENs were comprehensively and quantitatively analysed and were subsequently compared with those in PDACs. A principal component analysis revealed that the tissue immune profile is related to tumour histology, with distinct groups being observed for NETs, NECs, and PDACs. While NECs and some PDACs had hot immune microenvironments with abundant TILs, NETs had a cold immune microenvironment with few TILs. Moreover, in NETs, the numbers of intraepithelial PD-1high T cells and PD-L1high Type-II macrophages were elevated according to the grade. Univariate analysis revealed that lymph node metastasis, grade, stage, PD-1high T cells, and PD-L1high Type-II macrophages were predictors for recurrence-free survival (RFS), while grade and PD-1high T cells were prognostic factors for overall survival (OS). We also showed that PD-1high T cells and PD-L1high Type-II macrophages were associated with worse outcome in pNENs. Our results support the WHO 2017 tumour classification criteria, which distinguish between G3 NETs and NECs.
登录
查看更多内容
DOI：
10.1097/pas.0b013e3182417d36
发表时间：
2012-02
期刊：
The American journal of surgical pathology
影响因子：
--
作者：
Yachida S;Vakiani E;White CM;Zhong Y;Saunders T;Morgan R;de Wilde RF;Maitra A;Hicks J;Demarzo AM;Shi C;Sharma R;Laheru D;Edil BH;Wolfgang CL;Schulick RD;Hruban RH;Tang LH;Klimstra DS;Iacobuzio-Donahue CA
通讯作者：
Iacobuzio-Donahue CA
影响因子：
3.3
作者：
Igari, Fumie;Sato, Eiichi;Saito, Mitsue
通讯作者：
Saito, Mitsue
胰腺神经内分泌肿瘤中经常改变DAXX/ATRX，MEN1和MTOR途径基因。
DOI：
10.1126/science.1200609
发表时间：
2011-03-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Jiao Y;Shi C;Edil BH;de Wilde RF;Klimstra DS;Maitra A;Schulick RD;Tang LH;Wolfgang CL;Choti MA;Velculescu VE;Diaz LA Jr;Vogelstein B;Kinzler KW;Hruban RH;Papadopoulos N
通讯作者：
Papadopoulos N
影响因子：
64.8
作者：
Biankin, Andrew V.;Waddell, Nicola;Kassahn, Karin S.;Gingras, Marie-Claude;Muthuswamy, Lakshmi B.;Johns, Amber L.;Miller, David K.;Wilson, Peter J.;Patch, Ann-Marie;Wu, Jianmin;Chang, David K.;Cowley, Mark J.;Gardiner, Brooke B.;Song, Sarah;Harliwong, Ivon;Idrisoglu, Senel;Nourse, Craig;Nourbakhsh, Ehsan;Manning, Suzanne;Wani, Shivangi;Gongora, Milena;Pajic, Marina;Scarlett, Christopher J.;Gill, Anthony J.;Pinho, Andreia V.;Rooman, Ilse;Anderson, Matthew;Holmes, Oliver;Leonard, Conrad;Taylor, Darrin;Wood, Scott;Xu, Qinying;Nones, Katia;Fink, J. Lynn;Christ, Angelika;Bruxner, Tim;Cloonan, Nicole;Kolle, Gabriel;Newell, Felicity;Pinese, Mark;Mead, R. Scott;Humphris, Jeremy L.;Kaplan, Warren;Jones, Marc D.;Colvin, Emily K.;Nagrial, Adnan M.;Humphrey, Emily S.;Chou, Angela;Chin, Venessa T.;Chantrill, Lorraine A.;Mawson, Amanda;Samra, Jaswinder S.;Kench, James G.;Lovell, Jessica A.;Daly, Roger J.;Merrett, Neil D.;Toon, Christopher;Epari, Krishna;Nguyen, Nam Q.;Barbour, Andrew;Zeps, Nikolajs;Kakkar, Nipun;Zhao, Fengmei;Wu, Yuan Qing;Wang, Min;Muzny, Donna M.;Fisher, William E.;Brunicardi, F. Charles;Hodges, Sally E.;Reid, Jeffrey G.;Drummond, Jennifer;Chang, Kyle;Han, Yi;Lewis, Lora R.;Dinh, Huyen;Buhay, Christian J.;Beck, Timothy;Timms, Lee;Sam, Michelle;Begley, Kimberly;Brown, Andrew;Pai, Deepa;Panchal, Ami;Buchner, Nicholas;De Borja, Richard;Denroche, Robert E.;Yung, Christina K.;Serra, Stefano;Onetto, Nicole;Mukhopadhyay, Debabrata;Tsao, Ming-Sound;Shaw, Patricia A.;Petersen, Gloria M.;Gallinger, Steven;Hruban, Ralph H.;Maitra, Anirban;Iacobuzio-Donahue, Christine A.;Schulick, Richard D.;Wolfgang, Christopher L.;Morgan, Richard A.;Lawlor, Rita T.;Capelli, Paola;Corbo, Vincenzo;Scardoni, Maria;Tortora, Giampaolo;Tempero, Margaret A.;Mann, Karen M.;Jenkins, Nancy A.;Perez-Mancera, Pedro A.;Adams, David J.;Largaespada, David A.;Wessels, Lodewyk F. A.;Rust, Alistair G.;Stein, Lincoln D.;Tuveson, David A.;Copeland, Neal G.;Musgrove, Elizabeth A.;Scarpa, Aldo;Eshleman, James R.;Hudson, Thomas J.;Sutherland, Robert L.;Wheeler, David A.;Pearson, John V.;McPherson, John D.;Gibbs, Richard A.;Grimmond, Sean M.
通讯作者：
Grimmond, Sean M.
影响因子：
3.9
作者：
Kim ST;Ha SY;Lee S;Ahn S;Lee J;Park SH;Park JO;Lim HY;Kang WK;Kim KM;Park YS
通讯作者：
Park YS