The expression and prognostic value of toll-like receptors (TLRs) in pancreatic cancer patients treated with neoadjuvant therapy.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2022
Historique:
received: 29 04 2021
accepted: 15 04 2022
entrez: 10 5 2022
pubmed: 11 5 2022
medline: 14 5 2022
Statut: epublish

Résumé

Toll-like receptors (TLRs) play a pivotal role in the immune system and carcinogenesis. There is no research on TLR expression and association with survival among preoperatively treated pancreatic cancer patients. We studied the expression intensity and prognostic value of TLRs in pancreatic cancer patients treated with neoadjuvant therapy (NAT) and compared the results to patients undergoing upfront surgery (US). Between 2000 and 2015, 71 borderline resectable patients were treated with NAT and surgery and 145 resectable patients underwent upfront surgery at Helsinki University Hospital, Finland. We immunostained TLRs 1-5, 7, and 9 on sections of tissue-microarray. We classified TLR expression as 0 (negative), 1 (mild), 2 (moderate), or 3 (strong) and divided into high (2-3) and low (0-1) expression for statistical purposes. Among TLRs 1, 3, and 9 (TLR1 81% vs 70%, p = 0.008; TLR3 92% vs 68%, p = 0.001; TLR9 cytoplasmic 83% vs 42%, p<0.001; TLR9 membranous 53% vs 25%, p = 0.002) NAT patients exhibited a higher immunopositivity score more frequently than patients undergoing upfront surgery. Among NAT patients, a high expression of TLR1 [Hazards ratio (HR) 0.48, p<0.05] associated with a longer postoperative survival, whereas among US patients, high expression of TLR5 (HR 0.64, p<0.05), TLR7 (HR 0.59, p<0.01, and both TLR7 and TLR9 (HR 0.5, p<0.01) predicted a favorable postoperative outcome in separate analysis adjusted for background variables. We found higher immunopositive intensities among TLRs 1, 3, and 9 in NAT patients. A high TLR1 expression associated with a longer survival among NAT patients, however, among US patients, high expression intensity of TLR5 and TLR7 predicted a favorable postoperative outcome in the adjusted analysis.

Identifiants

pubmed: 35536778
doi: 10.1371/journal.pone.0267792
pii: PONE-D-21-14223
pmc: PMC9089880
doi:

Substances chimiques

Toll-Like Receptor 1 0
Toll-Like Receptor 5 0
Toll-Like Receptor 7 0
Toll-Like Receptor 9 0
Toll-Like Receptors 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0267792

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Anna Maria Nurmi (AM)

Department of Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.

Jaana Hagström (J)

Department of Pathology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
Department of Oral Pathology and Radiology, University of Turku, Turku, Finland.

Harri Mustonen (H)

Department of Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.

Hanna Seppänen (H)

Department of Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
Translational Cancer Medicine Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Caj Haglund (C)

Department of Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
Translational Cancer Medicine Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

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Classifications MeSH