Nizri Eran, Bar-David Shoshi, Aizic Asaf, Sternbach Neta, Lahat Guy, Wolf Ido, Klausner Joseph
Institute of Pathology, Tel-Aviv Sourasky Medical Center, Tel-Aviv.
Department of Internal Medicine D, Rabin Medical Center, Beilinson Hospital, Petah Tikva.
Pancreas. 2019 Mar;48(3):367-373. doi: 10.1097/MPA.0000000000001261.
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a peritumoral proliferation of fibroblasts and extracellular matrix production known as desmoplasia. We aimed to study desmoplasia in PDAC lymph node (LN) metastases.
We evaluated LNs from 66 patients with PDAC and LN metastases. We used immunohistochemistry and real-time polymerase chain reaction to phenotype the desmoplastic response.
Desmoplasia was identified in 57% of patients with LN metastases (Des+). Cancer-associated fibroblasts (CAFs) in Des+ expressed α-smooth muscle actin and collagen 11A1. The latter expression was present only in CAFs but not in LN stroma or in LN metastases without desmoplasia (Des-). Desmoplasia was associated with upregulation of transforming growth factor β messenger RNA. Whereas numbers of CD8+ in tumor vicinity were not different between Des+ and Des- patients (78 [standard deviation {SD}, 57] vs 92 [SD, 52], P = 0.48, respectively), the numbers of GATA-3+ cells, a marker of T-helper 2 immune response was significantly increased (3.7 [SD, 6.3] for Des+ vs 1.3 [SD, 2.7] for Des-, P < 0.05).
Lymph node desmoplasia is associated with CAF pattern activation and Th2 infiltration. Therapeutic modulation of desmoplasia may be relevant in the metastatic phase and influence antitumor immune response.
胰腺导管腺癌（PDAC）的特征是肿瘤周围成纤维细胞增殖和细胞外基质产生，即所谓的促结缔组织增生。我们旨在研究PDAC淋巴结（LN）转移灶中的促结缔组织增生情况。
我们评估了66例伴有LN转移的PDAC患者的LN。我们使用免疫组织化学和实时聚合酶链反应对促结缔组织增生反应进行表型分析。
在57%的LN转移患者（Des+）中发现了促结缔组织增生。Des+中的癌症相关成纤维细胞（CAF）表达α平滑肌肌动蛋白和胶原蛋白11A1。后一种表达仅存在于CAF中，而不存在于LN基质或无促结缔组织增生（Des-）的LN转移灶中。促结缔组织增生与转化生长因子β信使核糖核酸的上调相关。虽然Des+和Des-患者肿瘤附近的CD8+细胞数量没有差异（分别为78 [标准差{SD}，57]和92 [SD，52]，P = 0.48），但T辅助2免疫反应标志物GATA-3+细胞的数量显著增加（Des+为3.7 [SD，6.3]，Des-为1.3 [SD，2.7]，P < 0.05）。
淋巴结促结缔组织增生与CAF模式激活和Th2浸润相关。促结缔组织增生反应的治疗性调节在转移阶段可能具有相关性，并影响抗肿瘤免疫反应。
