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解析食管腺癌的炎症肿瘤微环境:肥大细胞和 NK 细胞是有利的预后因素,并与病变范围较小相关

英文原题:Dissecting the inflammatory tumor microenvironment of esophageal adenocarcinoma: mast cells and natural killer cells are favorable prognostic factors and associated with less extensive disease.

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Dissecting the inflammatory tumor microenvironment of esophageal adenocarcinoma: mast cells and natural killer cells are favorable prognostic factors and associated with less extensive disease.

PubMed 2023/02/24(内容时间) J Cancer Res Clin Oncol Q2 · IF 3.3(JCR 2025)

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研究概要

我们的结果表明,肥大细胞、NK 细胞及其他所评估的免疫细胞在 EAC 肿瘤微环境中扮演着复杂而重要的角色。因此,这些发现是朝着更好地理解该癌症类型中免疫细胞环境及其潜在治疗意义迈出的又一步。

研究思路结论见上方概要

食管腺癌(EAC)仍然是一种具有挑战性和致死性的癌症类型。正如免疫检查点抑制剂所取得的成功所证明的那样,肿瘤相关免疫细胞和肿瘤微环境(TME)是新的治疗方法有前景的靶点。然而,对食管癌中TME的了解仍然有限,需要进一步研究。

共纳入900多例EAC样本,包括接受初次手术和新辅助(放)化疗的患者。对肥大细胞(MC)、NK 细胞(NK细胞)、浆细胞(PC)和嗜酸性细胞(EC)的免疫细胞浸润进行半定量评估,并与组织病理学参数和总生存期(OS)进行相关性分析。

四种免疫细胞的高存在率均与较局限的肿瘤分期和较低的淋巴结转移频率显著相关,就NK细胞而言,还与较少的远处转移相关。MC和NK细胞的存在与总队列(MC:p < 0.001;NK细胞:p = 0.004)及未接受新辅助治疗患者(MC:p < 0.001;NK细胞:p = 0.01)的OS延长呈有利相关。NK细胞是总队列(p = 0.007)和未治疗亚组(p = 0.04)的有利预后因素。此外,MC是淋巴结转移患者(p = 0.009)的有利预后因素。

展开英文摘要原文

Esophageal adenocarcinoma (EAC) remains a challenging and lethal cancer entity. A promising target for new therapeutic approaches, as demonstrated by the success of immune checkpoint inhibitors, are tumor-associated immune cells and the tumor microenvironment (TME). However, the understanding of the TME in esophageal cancer remains limited and requires further investigation.

Over 900 EAC samples were included, including patients treated with primary surgery and neoadjuvant (radio-)chemotherapy. The immune cell infiltrates of mast cells (MC), natural killer cells (NK cells), plasma cells (PC), and eosinophilic cells (EC) were assessed semi-quantitatively and correlated with histopathological parameters and overall survival (OS).

A high presence of all four immune cell types significantly correlated with a less extensive tumor stage and a lower frequency of lymph node metastasis, and, in case of NK cells, with less distant metastasis. The presence of MC and NK cells was favorably associated with a prolonged OS in the total cohort (MC: p < 0.001; NK cells: p = 0.004) and patients without neoadjuvant treatment (MC: p < 0.001; NK cells: p = 0.01). NK cells were a favorable prognostic factor in the total cohort (p = 0.007) and in the treatment-naïve subgroup (p = 0.04). Additionally, MC were a favorable prognostic factor in patients with lymph node metastasis (p = 0.009).

Our results indicate a complex and important role of mast cells, NK cells, and the other assessed immune cells in the tumor microenvironment of EAC. Therefore, they are one further step to a better understanding of the immune cell environment and the potential therapeutic implications in this cancer entity.

论文信息

作者
Dos Santos Cunha AC、Simon AG、Zander T、Buettner R、Bruns CJ、Schroeder W、Gebauer F、Quaas A
第一作者单位
Institute of Pathology, University Hospital Cologne, Medical Faculty, University of Cologne, Kerpener Str. 62, DE-50937, Cologne, Germany.United States
通讯作者单位
Institute of Pathology, University Hospital Cologne, Medical Faculty, University of Cologne, Kerpener Str. 62, DE-50937, Cologne, Germany. adrian.simon@uk-koeln.de.United States
期刊
Journal of cancer research and clinical oncology2023 Aug
原文标识
PubMed 36826594 · DOI 10.1007/s00432-023-04650-0