Multiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes, Cancer-Associated Fibroblasts, and CD200 in Pancreatic Cancer

Pancreatic cancer is marked by a desmoplastic tumor microenvironment and low tumor immunogenicity, making it difficult for immunotherapy drugs to improve outcomes for patients. Tumor-infiltrating lymphocytes (TILs) and cancer-associated fibroblasts (CAFs) are seen in the tumor microenvironment of pa...

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Autores principales:	Tyler MacNeil, Ioannis A. Vathiotis, Saba Shafi, Thazin Nwe Aung, Jon Zugazagoitia, Aaron M. Gruver, Kyla Driscoll, David L. Rimm
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	PDAC immunotherapy lymphocytes fibroblasts CD200 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/deb20120a8434c9b8d33d3559534c68e
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spelling	oai:doaj.org-article:deb20120a8434c9b8d33d3559534c68e2021-11-11T15:33:45ZMultiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes, Cancer-Associated Fibroblasts, and CD200 in Pancreatic Cancer10.3390/cancers132155012072-6694https://doaj.org/article/deb20120a8434c9b8d33d3559534c68e2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5501https://doaj.org/toc/2072-6694Pancreatic cancer is marked by a desmoplastic tumor microenvironment and low tumor immunogenicity, making it difficult for immunotherapy drugs to improve outcomes for patients. Tumor-infiltrating lymphocytes (TILs) and cancer-associated fibroblasts (CAFs) are seen in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma (PDAC). In this work, we sought to characterize the expression levels and potential prognostic value of TILs (CD4, CD8, and CD20) and CAFs (Thy-1, FAP, and SMA) in a large retrospective cohort of PDAC patients. Additionally, we investigated the expression levels and prognostic significance of CD200, an immunoinhibitory protein that has shown interest as a potential target for immune checkpoint blockade. We measured the expression levels of these seven proteins with multiplexed immunofluorescence staining and quantitative immunofluorescence (QIF). We found CD8 and FAP to be independent predictors of progression-free survival and overall survival. CD200 was found to be heterogeneously expressed in both the tumor and stromal compartments of PDAC, with the majority of patients having positive stromal expression and negative tumor expression. This work demonstrates the potential clinical utility of CD8 and FAP in PDAC patients, and it sheds light on the expression patterns of CD200 in pancreatic cancer as the protein is being tested as a target for immune checkpoint blockade.Tyler MacNeilIoannis A. VathiotisSaba ShafiThazin Nwe AungJon ZugazagoitiaAaron M. GruverKyla DriscollDavid L. RimmMDPI AGarticlePDACimmunotherapylymphocytesfibroblastsCD200Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5501, p 5501 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	PDAC immunotherapy lymphocytes fibroblasts CD200 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	PDAC immunotherapy lymphocytes fibroblasts CD200 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Tyler MacNeil Ioannis A. Vathiotis Saba Shafi Thazin Nwe Aung Jon Zugazagoitia Aaron M. Gruver Kyla Driscoll David L. Rimm Multiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes, Cancer-Associated Fibroblasts, and CD200 in Pancreatic Cancer
description	Pancreatic cancer is marked by a desmoplastic tumor microenvironment and low tumor immunogenicity, making it difficult for immunotherapy drugs to improve outcomes for patients. Tumor-infiltrating lymphocytes (TILs) and cancer-associated fibroblasts (CAFs) are seen in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma (PDAC). In this work, we sought to characterize the expression levels and potential prognostic value of TILs (CD4, CD8, and CD20) and CAFs (Thy-1, FAP, and SMA) in a large retrospective cohort of PDAC patients. Additionally, we investigated the expression levels and prognostic significance of CD200, an immunoinhibitory protein that has shown interest as a potential target for immune checkpoint blockade. We measured the expression levels of these seven proteins with multiplexed immunofluorescence staining and quantitative immunofluorescence (QIF). We found CD8 and FAP to be independent predictors of progression-free survival and overall survival. CD200 was found to be heterogeneously expressed in both the tumor and stromal compartments of PDAC, with the majority of patients having positive stromal expression and negative tumor expression. This work demonstrates the potential clinical utility of CD8 and FAP in PDAC patients, and it sheds light on the expression patterns of CD200 in pancreatic cancer as the protein is being tested as a target for immune checkpoint blockade.
format	article
author	Tyler MacNeil Ioannis A. Vathiotis Saba Shafi Thazin Nwe Aung Jon Zugazagoitia Aaron M. Gruver Kyla Driscoll David L. Rimm
author_facet	Tyler MacNeil Ioannis A. Vathiotis Saba Shafi Thazin Nwe Aung Jon Zugazagoitia Aaron M. Gruver Kyla Driscoll David L. Rimm
author_sort	Tyler MacNeil
title	Multiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes, Cancer-Associated Fibroblasts, and CD200 in Pancreatic Cancer
title_short	Multiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes, Cancer-Associated Fibroblasts, and CD200 in Pancreatic Cancer
title_full	Multiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes, Cancer-Associated Fibroblasts, and CD200 in Pancreatic Cancer
title_fullStr	Multiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes, Cancer-Associated Fibroblasts, and CD200 in Pancreatic Cancer
title_full_unstemmed	Multiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes, Cancer-Associated Fibroblasts, and CD200 in Pancreatic Cancer
title_sort	multiplex quantitative analysis of tumor-infiltrating lymphocytes, cancer-associated fibroblasts, and cd200 in pancreatic cancer
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/deb20120a8434c9b8d33d3559534c68e
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Multiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes, Cancer-Associated Fibroblasts, and CD200 in Pancreatic Cancer

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