Prognostic value, localization and correlation of PD-1/PD-L1, CD8 and FOXP3 with the desmoplastic stroma in pancreatic ductal adenocarcinoma.
Prognostic value, localization and correlation of PD-1/PD-L1, CD8 and FOXP3 with the desmoplastic stroma in pancreatic ductal adenocarcinoma.
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DOI：
10.18632/oncotarget.10038
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发表时间：
2016-07-05
期刊：
影响因子：
--
通讯作者：
Fokas E
中科院分区：
文献类型：
--
作者：
Diana A;Wang LM;D'Costa Z;Allen P;Azad A;Silva MA;Soonawalla Z;Liu S;McKenna WG;Muschel RJ;Fokas E
我们研究了程序性细胞死亡-1（PD-1）及其配体（PD-L1）与CD 8+肿瘤浸润淋巴细胞（TIL）和FOXP 3 + TCLs在接受辅助化疗的可切除胰腺导管腺癌（PDAC）样本中的预后价值。对来自145例胰腺切除术的全封片FFPE组织切片进行PD-1、PD-L1、CD 8和FOXP 3的免疫组化染色。它们的表达与临床病理学特征、总生存期（OS）、无进展生存期（PFS）、局部无进展生存期（LPFS）和无远处转移生存期（DMFS）、基质密度（苏木精-伊红）和活性（α-平滑肌肌动蛋白）以及肿瘤内淋巴聚集体相关。平均随访20个月（范围：2-69个月）后，中位OS为21个月。在多变量分析中，高PD-1+ TIL表达与更好的OS（p = 0.049）、LPFS（p = 0.017）和DMFS（p = 0.021）相关。在CD 8 + TIL中观察到类似的发现，而FOXP 3和PD-L1缺乏预后意义。尽管TIL的分布是不均匀的，但高间质密度的肿瘤比松散密度的间质具有更高的CD 8 + TIL浸润，反之亦然（p < 0.001），而未发现与间质活性相关。60例（41.4%）肿瘤含有淋巴聚集体，PD-1+ TIL的存在与更好的OS（p = 0.030）、LPFS（p = 0.025）和DMFS（p = 0.033）相关，而CD 8 + TIL仅与更优的上级LPFS相关（p = 0.039）。PD-1+和CD 8 + TIL是接受辅助化疗的PDAC患者的独立预后标志物。我们的研究为PD-1/PD-L1在促结缔组织增生基质中的作用提供了重要的见解，并有助于指导未来PDAC的免疫治疗。
We examined the prognostic value of programmed cell death-1 (PD-1) and its ligand (PD-L1) together with CD8+ tumor-infiltrating lymphocytes (TILs) and FOXP3+ Tregs in resectable pancreatic ductal adenocarcinoma (PDAC) samples treated with adjuvant chemotherapy. Whole-mount FFPE tissue sections from 145 pancreatectomies were immunohistochemically stained for PD-1, PD-L1, CD8 and FOXP3. Their expression was correlated with clinicopathological characteristics, and overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS), in the context of stroma density (haematoxylin-eosin) and activity (alpha-smooth muscle actin) and in regard to intratumoral lymphoid aggregates. The median OS was 21 months after a mean follow-up of 20 months (range, 2-69 months). In multivariate analysis, high PD-1+ TILs expression was associated with better OS (p = 0.049), LPFS (p = 0.017) and DMFS (p = 0.021). Similar findings were observed for CD8+ TILs, whereas FOXP3 and PD-L1 lacked prognostic significance. Although TIL distribution was heterogeneous, tumors of high stroma density had higher infiltration of CD8+ TILs than loose density stroma and vice versa (p < 0.001), whereas no correlation was found with stromal activity. Sixty (41.4%) tumors contained lymphoid aggregates and the presence of PD-1+ TILs was associated with better OS (p = 0.030), LPFS (p = 0.025) and DMFS (p = 0.033), whereas CD8+ TILs only correlated with superior LPFS (p = 0.039). PD-1+ and CD8+ TILs constitute independent prognostic markers in patients with PDAC treated with adjuvant chemotherapy. Our study provides important insight on the role of PD-1/PD-L1 in the context of desmoplastic stroma and could help guide future immunotherapies in PDAC.
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影响因子：
8.8
作者：
Nedergaard BS;Ladekarl M;Thomsen HF;Nyengaard JR;Nielsen K
通讯作者：
Nielsen K
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：
8.8
作者：
Balermpas, P;Michel, Y;Wagenblast, J;Seitz, O;Weiss, C;Rodel, F;Rodel, C;Fokas, E
通讯作者：
Fokas, E
DOI：
10.1073/pnas.1320318110
发表时间：
2013-12-10
影响因子：
11.1
作者：
Feig, Christine;Jones, James O.;Fearon, Douglas T.
通讯作者：
Fearon, Douglas T.
影响因子：
29.4
作者：
Ene-Obong A;Clear AJ;Watt J;Wang J;Fatah R;Riches JC;Marshall JF;Chin-Aleong J;Chelala C;Gribben JG;Ramsay AG;Kocher HM
通讯作者：
Kocher HM