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

Alberto D'Angelo, Navid Sobhani, Giandomenico Roviello, Stefan Bagby, Deborah Bonazza, Cristina Bottin, Fabiola Giudici, Fabrizio Zanconati, Nicolo De Manzini, Alessandra Guglielmi, Daniele Generali

Research output: Contribution to journalArticle

Abstract

BACKGROUND: We investigated the correlation between pancreatic ductal adenocarcinoma patient prognosis and the presence of tumour infiltrating lymphocytes and expression of 521 immune system genes.

METHODS: Intratumoural CD3+, CD8+, and CD20+ lymphocytes were examined by immunohistochemistry in 12 PDAC patients with different outcomes who underwent pancreaticoduodenectomy. 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 receptor superfamily); CD4, CD37, FOXP3, PTPRC (B cell and T cell signalling); IRF5, IRF8, STAT1, TFE3 (transcription factors); ANP32B, CCND3 (cell cycle); BTK (B cell development); 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 expression 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.

Original languageEnglish
Article numbere0219566
JournalPLoS ONE
Volume14
Issue number8
DOIs
Publication statusPublished - 5 Aug 2019

Cite this

Tumour infiltrating lymphocytes and immune-related genes as predictors of outcome in pancreatic adenocarcinoma. / D'Angelo, Alberto; Sobhani, Navid; Roviello, Giandomenico; Bagby, Stefan; Bonazza, Deborah; Bottin, Cristina; Giudici, Fabiola; Zanconati, Fabrizio; De Manzini, Nicolo; Guglielmi, Alessandra; Generali, Daniele.

In: PLoS ONE, Vol. 14, No. 8, e0219566, 05.08.2019.

Research output: Contribution to journalArticle

D'Angelo, A, Sobhani, N, Roviello, G, Bagby, S, Bonazza, D, Bottin, C, Giudici, F, Zanconati, F, De Manzini, N, Guglielmi, A & Generali, D 2019, 'Tumour infiltrating lymphocytes and immune-related genes as predictors of outcome in pancreatic adenocarcinoma', PLoS ONE, vol. 14, no. 8, e0219566. https://doi.org/10.1371/journal.pone.0219566
D'Angelo, Alberto ; Sobhani, Navid ; Roviello, Giandomenico ; Bagby, Stefan ; Bonazza, Deborah ; Bottin, Cristina ; Giudici, Fabiola ; Zanconati, Fabrizio ; De Manzini, Nicolo ; Guglielmi, Alessandra ; Generali, Daniele. / Tumour infiltrating lymphocytes and immune-related genes as predictors of outcome in pancreatic adenocarcinoma. In: PLoS ONE. 2019 ; Vol. 14, No. 8.
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AU - Sobhani, Navid

AU - Roviello, Giandomenico

AU - Bagby, Stefan

AU - Bonazza, Deborah

AU - Bottin, Cristina

AU - Giudici, Fabiola

AU - Zanconati, Fabrizio

AU - De Manzini, Nicolo

AU - Guglielmi, Alessandra

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AB - BACKGROUND: We investigated the correlation between pancreatic ductal adenocarcinoma patient prognosis and the presence of tumour infiltrating lymphocytes and expression of 521 immune system genes.METHODS: Intratumoural CD3+, CD8+, and CD20+ lymphocytes were examined by immunohistochemistry in 12 PDAC patients with different outcomes who underwent pancreaticoduodenectomy. 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 receptor superfamily); CD4, CD37, FOXP3, PTPRC (B cell and T cell signalling); IRF5, IRF8, STAT1, TFE3 (transcription factors); ANP32B, CCND3 (cell cycle); BTK (B cell development); 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 expression 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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