Prognostic value of tumor-associated N1/N2 neutrophil plasticity in patients following radical resection of pancreas ductal adenocarcinoma.
Tumor Biomarkers
Tumor Microenvironment
Journal
Journal for immunotherapy of cancer
ISSN: 2051-1426
Titre abrégé: J Immunother Cancer
Pays: England
ID NLM: 101620585
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
accepted:
03
11
2022
entrez:
5
1
2023
pubmed:
6
1
2023
medline:
7
1
2023
Statut:
ppublish
Résumé
As an integral part of the tumor microenvironment (TME), tumor-associated neutrophils play a crucial role in tumor development. The objective of this study was to investigate the plasticity of tumor-associated N1 and N2 neutrophils in the TME of pancreatic ductal adenocarcinoma (PDAC), along with its impact on survival and association with immune infiltrations. The primary and validation cohorts including 90 radical resection patients from September 2012 to May 2016 and 29 radical resection patients from September 2018 to October 2019, respectively, with complete survival data, were enrolled. Immunofluorescence staining was used to identify tumor-associated N1 and N2 neutrophils, and the N1/N2 ratio was used to evaluate N1 and N2 plasticity. Thereafter, the association between tumor-associated N1/N2 neutrophil plasticity, clinical features, and immune infiltrations was investigated. There was a significant increase in tumor-associated N2 neutrophils compared with tumor-associated N1 neutrophils. Low N1/N2 ratios were associated with the poorer differentiation of tumors, easier lymph node metastases, and a higher TNM stage. The median overall survival (OS) and recurrence-free survival (RFS) of the high tumor-associated N1 neutrophil group were significantly longer than those of the low group, while the tumor-associated N2 neutrophils played an opposite role. The multivariable analysis revealed that a high N1/N2 ratio was a significant prognostic indicator for OS and RFS. In addition, tumor-associated N1/N2 neutrophils showed an opposite correlation with tumor-infiltrating CD8 The plasticity of tumor-associated N1/N2 neutrophils was identified as a crucial prognostic indicator that might reflect the TME and immune escape in patients with PDAC. On further investigation and validation, our findings may be used to further stratify patients with varying prognoses to optimize treatment.
Sections du résumé
BACKGROUND
As an integral part of the tumor microenvironment (TME), tumor-associated neutrophils play a crucial role in tumor development. The objective of this study was to investigate the plasticity of tumor-associated N1 and N2 neutrophils in the TME of pancreatic ductal adenocarcinoma (PDAC), along with its impact on survival and association with immune infiltrations.
METHODS
The primary and validation cohorts including 90 radical resection patients from September 2012 to May 2016 and 29 radical resection patients from September 2018 to October 2019, respectively, with complete survival data, were enrolled. Immunofluorescence staining was used to identify tumor-associated N1 and N2 neutrophils, and the N1/N2 ratio was used to evaluate N1 and N2 plasticity. Thereafter, the association between tumor-associated N1/N2 neutrophil plasticity, clinical features, and immune infiltrations was investigated.
RESULTS
There was a significant increase in tumor-associated N2 neutrophils compared with tumor-associated N1 neutrophils. Low N1/N2 ratios were associated with the poorer differentiation of tumors, easier lymph node metastases, and a higher TNM stage. The median overall survival (OS) and recurrence-free survival (RFS) of the high tumor-associated N1 neutrophil group were significantly longer than those of the low group, while the tumor-associated N2 neutrophils played an opposite role. The multivariable analysis revealed that a high N1/N2 ratio was a significant prognostic indicator for OS and RFS. In addition, tumor-associated N1/N2 neutrophils showed an opposite correlation with tumor-infiltrating CD8
CONCLUSION
The plasticity of tumor-associated N1/N2 neutrophils was identified as a crucial prognostic indicator that might reflect the TME and immune escape in patients with PDAC. On further investigation and validation, our findings may be used to further stratify patients with varying prognoses to optimize treatment.
Identifiants
pubmed: 36600557
pii: jitc-2022-005798
doi: 10.1136/jitc-2022-005798
pmc: PMC9730407
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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