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The paratumoral immune cell signature reveals the potential for the implementation of immunotherapy in esophageal carcinoma patients
Z. Strizova, M. Snajdauf, D. Stakheev, P. Taborska, J. Vachtenheim, J. Biskup, R. Lischke, J. Bartunkova, D. Smrz,
Language English Country Germany
Document type Journal Article
Grant support
GA UK No. 364218
Univerzita Karlova v Praze
PRIMUS/MED/12
Univerzita Karlova v Praze
AZV 16-28135A
Ministerstvo Zdravotnictví Ceské Republiky
- MeSH
- Adenocarcinoma immunology pathology therapy MeSH
- fas Receptor immunology MeSH
- Killer Cells, Natural immunology pathology MeSH
- CD4-Positive T-Lymphocytes immunology pathology MeSH
- CD8-Positive T-Lymphocytes immunology pathology MeSH
- Immunotherapy methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Lymph Nodes immunology pathology MeSH
- Lymphocytes immunology pathology MeSH
- Esophageal Neoplasms immunology pathology therapy MeSH
- Aged MeSH
- Esophageal Squamous Cell Carcinoma immunology pathology therapy MeSH
- Case-Control Studies MeSH
- T-Lymphocyte Subsets immunology pathology MeSH
- Lymphocytes, Tumor-Infiltrating immunology pathology MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
PURPOSE: Esophageal cancer (EC) is one of the most lethal gastrointestinal malignancies. Immunotherapy is a promising treatment modality for this disease. However, broader implementation of EC immunotherapy has been discouraged because of insufficient understanding of tumor interactions with the immune system. As with other malignancies, the current research on EC focuses on deciphering the immune cell signatures within the tumor microenvironment. However, the disease-elicited immune cell profiles in the paratumoral compartments are largely unknown. METHODS: We examined the immune cell signatures in 62 tissue samples from 16 EC patients in different esophageal tissue compartments: tumor tissue, peritumoral tissue, healthy esophageal tissue, and adjacent lymph nodes. We analyzed the proportions and distribution patterns of NK cells and CD4+ and CD8+ T cells as well as their death receptor (FasR, FasR/DR3)-expressing subpopulations. The analyzed data were then compared and correlated with the patients' clinicopathological data. RESULTS: We found that the FasR+ NK cells, CD4+ and CD8+ T cells infiltrated lymph nodes at the lowest levels and that the FasR+DR3+ CD4+ T cells were enhanced in tumors. The comparisons with the clinicopathological data revealed a major impact of active smoking on the reduction in paratumoral NK cells and the upregulation of FasR in tumor-infiltrating NK and CD8+ T cells. The lymph node metastatic stage, tumor stage, and Mandard grade correlated with the compartmental proportions of the evaluated immune cells. CONCLUSION: The novel association of the disease state with tumoral and paratumoral immune cell signatures suggests new possibilities for personalized immunotherapy for EC patients.
References provided by Crossref.org
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- $a Strizova, Zuzana $u Department of Immunology, Second Faculty of Medicine, Charles University and University Hospital Motol, V Uvalu 84, Praha 5, 150 06, Prague, Czech Republic.
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- $a PURPOSE: Esophageal cancer (EC) is one of the most lethal gastrointestinal malignancies. Immunotherapy is a promising treatment modality for this disease. However, broader implementation of EC immunotherapy has been discouraged because of insufficient understanding of tumor interactions with the immune system. As with other malignancies, the current research on EC focuses on deciphering the immune cell signatures within the tumor microenvironment. However, the disease-elicited immune cell profiles in the paratumoral compartments are largely unknown. METHODS: We examined the immune cell signatures in 62 tissue samples from 16 EC patients in different esophageal tissue compartments: tumor tissue, peritumoral tissue, healthy esophageal tissue, and adjacent lymph nodes. We analyzed the proportions and distribution patterns of NK cells and CD4+ and CD8+ T cells as well as their death receptor (FasR, FasR/DR3)-expressing subpopulations. The analyzed data were then compared and correlated with the patients' clinicopathological data. RESULTS: We found that the FasR+ NK cells, CD4+ and CD8+ T cells infiltrated lymph nodes at the lowest levels and that the FasR+DR3+ CD4+ T cells were enhanced in tumors. The comparisons with the clinicopathological data revealed a major impact of active smoking on the reduction in paratumoral NK cells and the upregulation of FasR in tumor-infiltrating NK and CD8+ T cells. The lymph node metastatic stage, tumor stage, and Mandard grade correlated with the compartmental proportions of the evaluated immune cells. CONCLUSION: The novel association of the disease state with tumoral and paratumoral immune cell signatures suggests new possibilities for personalized immunotherapy for EC patients.
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