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CXCR4-CXCL12-CXCR7 and PD-1/PD-L1 in Pancreatic Cancer: CXCL12 Predicts Survival of Radically Resected Patients
Pancreatic ductal adenocarcinoma (PDAC) is currently the most deadly cancer. Although characterized by 5–20% of neoplastic cells in the highly fibrotic stroma, immunotherapy is not a valid option in PDAC treatment. As CXCR4-CXCL12 regulates tumor invasion and T-cell access and PD-1/PD-L1 controls im...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9655815/ https://www.ncbi.nlm.nih.gov/pubmed/36359736 http://dx.doi.org/10.3390/cells11213340 |
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author | D’Alterio, Crescenzo Giardino, Alessandro Scognamiglio, Giosuè Butturini, Giovanni Portella, Luigi Guardascione, Giuseppe Frigerio, Isabella Montella, Marco Gobbo, Stefano Martignoni, Guido Napolitano, Vincenzo De Vita, Ferdinando Tatangelo, Fabiana Franco, Renato Scala, Stefania |
author_facet | D’Alterio, Crescenzo Giardino, Alessandro Scognamiglio, Giosuè Butturini, Giovanni Portella, Luigi Guardascione, Giuseppe Frigerio, Isabella Montella, Marco Gobbo, Stefano Martignoni, Guido Napolitano, Vincenzo De Vita, Ferdinando Tatangelo, Fabiana Franco, Renato Scala, Stefania |
author_sort | D’Alterio, Crescenzo |
collection | PubMed |
description | Pancreatic ductal adenocarcinoma (PDAC) is currently the most deadly cancer. Although characterized by 5–20% of neoplastic cells in the highly fibrotic stroma, immunotherapy is not a valid option in PDAC treatment. As CXCR4-CXCL12 regulates tumor invasion and T-cell access and PD-1/PD-L1 controls immune tolerance, 76 PDACs were evaluated for CXCR4-CXCL12-CXCR7 and PD-1/PD-L1 in the epithelial and stromal component. Neoplastic CXCR4 and CXCL12 discriminated PDACs for recurrence-free survival (RFS), while CXCL12 and CXCR7 discriminated patients for cancer-specific survival (CSS). Interestingly, among patients with radical resection (R0), high tumor CXCR4 clustered patients with worse RFS, high CXCL12 identified poor prognostic patients for both RFS and CSS, while stromal lymphocytic-monocytic PD-L1 associated with improved RFS and CSS. PD-1 was only sporadically expressed (<1%) in focal lymphocyte infiltrate and does not impact prognosis. In multivariate analysis, tumoral CXCL12, perineural invasion, and AJCC lymph node status were independent prognostic factors for RFS; tumoral CXCL12, AJCC Stage, and vascular invasion were independent prognostic factors for CSS. CXCL12’s poor prognostic meaning was confirmed in an additional perspective-independent 13 fine-needle aspiration cytology advanced stage-PDACs. Thus, CXCR4-CXCL12 evaluation in PDAC identifies prognostic categories and could orient therapeutic approaches. |
format | Online Article Text |
id | pubmed-9655815 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96558152022-11-15 CXCR4-CXCL12-CXCR7 and PD-1/PD-L1 in Pancreatic Cancer: CXCL12 Predicts Survival of Radically Resected Patients D’Alterio, Crescenzo Giardino, Alessandro Scognamiglio, Giosuè Butturini, Giovanni Portella, Luigi Guardascione, Giuseppe Frigerio, Isabella Montella, Marco Gobbo, Stefano Martignoni, Guido Napolitano, Vincenzo De Vita, Ferdinando Tatangelo, Fabiana Franco, Renato Scala, Stefania Cells Article Pancreatic ductal adenocarcinoma (PDAC) is currently the most deadly cancer. Although characterized by 5–20% of neoplastic cells in the highly fibrotic stroma, immunotherapy is not a valid option in PDAC treatment. As CXCR4-CXCL12 regulates tumor invasion and T-cell access and PD-1/PD-L1 controls immune tolerance, 76 PDACs were evaluated for CXCR4-CXCL12-CXCR7 and PD-1/PD-L1 in the epithelial and stromal component. Neoplastic CXCR4 and CXCL12 discriminated PDACs for recurrence-free survival (RFS), while CXCL12 and CXCR7 discriminated patients for cancer-specific survival (CSS). Interestingly, among patients with radical resection (R0), high tumor CXCR4 clustered patients with worse RFS, high CXCL12 identified poor prognostic patients for both RFS and CSS, while stromal lymphocytic-monocytic PD-L1 associated with improved RFS and CSS. PD-1 was only sporadically expressed (<1%) in focal lymphocyte infiltrate and does not impact prognosis. In multivariate analysis, tumoral CXCL12, perineural invasion, and AJCC lymph node status were independent prognostic factors for RFS; tumoral CXCL12, AJCC Stage, and vascular invasion were independent prognostic factors for CSS. CXCL12’s poor prognostic meaning was confirmed in an additional perspective-independent 13 fine-needle aspiration cytology advanced stage-PDACs. Thus, CXCR4-CXCL12 evaluation in PDAC identifies prognostic categories and could orient therapeutic approaches. MDPI 2022-10-22 /pmc/articles/PMC9655815/ /pubmed/36359736 http://dx.doi.org/10.3390/cells11213340 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article D’Alterio, Crescenzo Giardino, Alessandro Scognamiglio, Giosuè Butturini, Giovanni Portella, Luigi Guardascione, Giuseppe Frigerio, Isabella Montella, Marco Gobbo, Stefano Martignoni, Guido Napolitano, Vincenzo De Vita, Ferdinando Tatangelo, Fabiana Franco, Renato Scala, Stefania CXCR4-CXCL12-CXCR7 and PD-1/PD-L1 in Pancreatic Cancer: CXCL12 Predicts Survival of Radically Resected Patients |
title | CXCR4-CXCL12-CXCR7 and PD-1/PD-L1 in Pancreatic Cancer: CXCL12 Predicts Survival of Radically Resected Patients |
title_full | CXCR4-CXCL12-CXCR7 and PD-1/PD-L1 in Pancreatic Cancer: CXCL12 Predicts Survival of Radically Resected Patients |
title_fullStr | CXCR4-CXCL12-CXCR7 and PD-1/PD-L1 in Pancreatic Cancer: CXCL12 Predicts Survival of Radically Resected Patients |
title_full_unstemmed | CXCR4-CXCL12-CXCR7 and PD-1/PD-L1 in Pancreatic Cancer: CXCL12 Predicts Survival of Radically Resected Patients |
title_short | CXCR4-CXCL12-CXCR7 and PD-1/PD-L1 in Pancreatic Cancer: CXCL12 Predicts Survival of Radically Resected Patients |
title_sort | cxcr4-cxcl12-cxcr7 and pd-1/pd-l1 in pancreatic cancer: cxcl12 predicts survival of radically resected patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9655815/ https://www.ncbi.nlm.nih.gov/pubmed/36359736 http://dx.doi.org/10.3390/cells11213340 |
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