Background: We investigated the correlation between pancreatic ductal adenocarcinoma patient progno- sis and the presence of tumour infiltrating lymphocytes and expression of 521 immune sys- tem genes. Methods: Intratumoural CD3+, CD8+, and CD20+ lymphocytes were examined by immunohistochem- istry in 12 PDAC patients with different outcomes who underwent pancreaticoduodenect- omy. The results were correlated with gene expression profile using the digital multiplexed NanoString nCounter analysis system (NanoString Technologies, Seattle, WA, USA). Results: Twenty immune system genes were significantly differentially expressed in patients with a good prognosis relative to patients with a worse prognosis: TLR2 and TLR7 (Toll-like recep- tor superfamily); CD4, CD37, FOXP3, PTPRC (B cell and T cell signalling); IRF5, IRF8, STAT1, TFE3 (transcription factors); ANP32B, CCND3 (cell cycle); BTK (B cell develop- ment); TNF, TNFRF1A (TNF superfamily); HCK (leukocyte function); C1QA (complement system); BAX, PNMA1 (apoptosis); IKBKE (NFκB pathway). Differential expression was more than twice log 2 for TLR7, TNF, C1QA, FOXP3, and CD37. Discussion: Tumour infiltrating lymphocytes were present at higher levels in samples from patients with better prognosis. Our findings indicate that tumour infiltrating lymphocyte levels and expres- sion level of the immune system genes listed above influence pancreatic ductal adenocarcinoma prognosis. This information could be used to improve selection of best responders to immune inhibitors.

Tumour infiltrating lymphocytes and immune-related genes as predictors of outcome in pancreatic adenocarcinoma

Sobhani, Navid
Data Curation
;
Roviello, Giandomenico
Supervision
;
Bonazza, Deborah
Conceptualization
;
Bottin, Cristina
Methodology
;
Giudici, Fabiola
Data Curation
;
Zanconati, Fabrizio
Conceptualization
;
De Manzini, Nicolo
Resources
;
Generali, Daniele
Conceptualization
2019-01-01

Abstract

Background: We investigated the correlation between pancreatic ductal adenocarcinoma patient progno- sis and the presence of tumour infiltrating lymphocytes and expression of 521 immune sys- tem genes. Methods: Intratumoural CD3+, CD8+, and CD20+ lymphocytes were examined by immunohistochem- istry in 12 PDAC patients with different outcomes who underwent pancreaticoduodenect- omy. The results were correlated with gene expression profile using the digital multiplexed NanoString nCounter analysis system (NanoString Technologies, Seattle, WA, USA). Results: Twenty immune system genes were significantly differentially expressed in patients with a good prognosis relative to patients with a worse prognosis: TLR2 and TLR7 (Toll-like recep- tor superfamily); CD4, CD37, FOXP3, PTPRC (B cell and T cell signalling); IRF5, IRF8, STAT1, TFE3 (transcription factors); ANP32B, CCND3 (cell cycle); BTK (B cell develop- ment); TNF, TNFRF1A (TNF superfamily); HCK (leukocyte function); C1QA (complement system); BAX, PNMA1 (apoptosis); IKBKE (NFκB pathway). Differential expression was more than twice log 2 for TLR7, TNF, C1QA, FOXP3, and CD37. Discussion: Tumour infiltrating lymphocytes were present at higher levels in samples from patients with better prognosis. Our findings indicate that tumour infiltrating lymphocyte levels and expres- sion level of the immune system genes listed above influence pancreatic ductal adenocarcinoma prognosis. This information could be used to improve selection of best responders to immune inhibitors.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11368/2948770
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