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

Author:

dos Santos Cunha Alyne Condurú,Simon Adrian Georg,Zander Thomas,Buettner Reinhard,Bruns Christiane Josephine,Schroeder Wolfgang,Gebauer Florian,Quaas Alexander

Abstract

Abstract Purpose 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. Methods 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). Results 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). Conclusion 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.

Funder

Universitätsklinikum Köln

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Oncology,General Medicine

Cited by 4 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Towards personalized management of early esophageal adenocarcinoma;Current Opinion in Gastroenterology;2024-04-11

2. Tumour microenvironment influences response to treatment in oesophageal adenocarcinoma;Frontiers in Immunology;2023-12-13

3. The Underappreciated Role of Eosinophils in Esophageal Cancer;Cellular and Molecular Gastroenterology and Hepatology;2023

4. Eosinophils Exert Antitumorigenic Effects in the Development of Esophageal Squamous Cell Carcinoma;Cellular and Molecular Gastroenterology and Hepatology;2023

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