Infiltrating pattern and prognostic value of tertiary lymphoid structures in resected non-functional pancreatic neuroendocrine tumors.
Infiltrating pattern and prognostic value of tertiary lymphoid structures in resected non-functional pancreatic neuroendocrine tumors.
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切除的非功能性胰腺神经内分泌肿瘤中三级淋巴结构的浸润模式及预后价值
DOI：
10.1136/jitc-2020-001188
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发表时间：
2020-10
影响因子：
10.9
通讯作者：
Liu L
中科院分区：
文献类型：
--
作者：
Zhang WH;Wang WQ;Han X;Gao HL;Xu SS;Li S;Li TJ;Xu HX;Li H;Ye LY;Lin X;Wu CT;Long J;Yu XJ;Liu L
研究背景三级淋巴样结构（TLS）与良好的生存率相关，在大多数实体瘤中起着关键作用。然而，TLS的研究缺乏1级或2级（G1/G2）非功能性胰腺神经内分泌肿瘤（NF-PanNET）的患者。本研究旨在研究TLS在G1/G2 NF-PanNET中的存在、细胞组成、与肿瘤浸润免疫细胞的相关性以及预后价值。方法采用H&E染色、免疫组化和/或多光谱荧光免疫组化方法对182例复旦大学队列患者和125例外部验证患者的肿瘤组织进行评估。结果在超过三分之一的G1/G2 NF-PanNETs患者中发现TLS，位于肿瘤周围，即肿瘤组织外或间质区域。TLS主要由具有生发中心的B细胞滤泡和具有树突状细胞的T细胞带组成。Kaplan-Meier分析显示TLS的存在与较长的无复发生存期（RFS，p<0.001）和总生存期（OS，p=0.001）相关，但TLS的数量没有预后意义。多变量Cox回归分析表明，TLS的存在、WHO分类和第8版美国癌症联合委员会（AJCC第8版）肿瘤淋巴结转移（TNM）分期是RFS（分别为p=0.004、p=0.001和p<0.001）和OS（分别为p=0.009、p=0.008和p=0.019）的独立预后因素。使用外部验证集确认了这些结果。最后，构建了一个包含TLS存在的诺模图，以预测切除的G1/G2 NF-PanNET的5年RFS的概率，这改进了当前的WHO分类和AJCC第8期TNM分期。结论TLS的存在是G1/G2期NF-PanNETs切除的一个独立和有利的预测因素，可能在肿瘤免疫生物学中发挥作用。
Background Tertiary lymphoid structures (TLS) are associated with favorable survival and play a critical role in most solid tumors. However, investigations of TLS are lacking in patients with grade 1 or grade 2 (G1/G2) non-functional pancreatic neuroendocrine tumors (NF-PanNETs). This study aimed to investigate the presence, cellular composition, association with tumor-infiltrating immune cells, and prognostic value of TLS in G1/G2 NF-PanNETs. Methods Tumor tissues from a 182-patient Fudan cohort and a 125-patient external validation set were assessed by H&E staining, immunohistochemistry, and/or multispectral fluorescent immunohistochemistry. Results TLS were identified in more than one-third of patients with G1/G2 NF-PanNETs and were located peritumorally, either just outside the tumor tissue or in the stromal area. TLS were mainly composed of B-cell follicles with germinal centers and T-cell zones with dendritic cells. Kaplan-Meier analyses showed that the presence of TLS correlated with both longer recurrence-free survival (RFS, p<0.001) and overall survival (OS, p=0.001), but the number of TLS had no prognostic significance. Multivariate Cox-regression analyses demonstrated that the presence of TLS, WHO classification, and 8th edition American Joint Committee on Cancer (AJCC8th) tumor-node-metastasis (TNM) stage were independent prognostic factors for RFS (p=0.004, p=0.001, and p<0.001, respectively) and OS (p=0.009, p=0.008, and p=0.019, respectively). These results were confirmed using an external validation set. Finally, a nomogram incorporating the presence of TLS was constructed to predict the probability of 5-year RFS of resected G1/G2 NF-PanNETs, which improved on the current WHO classification and AJCC8th TNM stage. Conclusions The presence of TLS is an independent and favorable predictor of resected G1/G2 NF-PanNETs, which may play a role in cancer immunobiology.
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影响因子：
32.4
作者：
Joshi NS;Akama-Garren EH;Lu Y;Lee DY;Chang GP;Li A;DuPage M;Tammela T;Kerper NR;Farago AF;Robbins R;Crowley DM;Bronson RT;Jacks T
通讯作者：
Jacks T
影响因子：
8.8
作者：
Ino Y;Yamazaki-Itoh R;Shimada K;Iwasaki M;Kosuge T;Kanai Y;Hiraoka N
通讯作者：
Hiraoka N
影响因子：
30.5
作者：
Finkin S;Yuan D;Stein I;Taniguchi K;Weber A;Unger K;Browning JL;Goossens N;Nakagawa S;Gunasekaran G;Schwartz ME;Kobayashi M;Kumada H;Berger M;Pappo O;Rajewsky K;Hoshida Y;Karin M;Heikenwalder M;Ben-Neriah Y;Pikarsky E
通讯作者：
Pikarsky E
影响因子：
7.3
作者：
Hiraoka N;Ino Y;Yamazaki-Itoh R
通讯作者：
Yamazaki-Itoh R
影响因子：
9
作者：
Landoni, Luca;Marchegiani, Giovanni;Bassi, Claudio
通讯作者：
Bassi, Claudio