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Interaction of immune checkpoint PD-1 and chemokine receptor 4 (CXCR4) promotes a malignant phenotype in pancreatic cancer cells

Despite recent therapeutic advances, pancreatic ductal adenocarcinoma (PDAC) remains a devastating disease with limited therapeutic options. Immune checkpoint inhibitors (ICIs) have demonstrated promising results in many cancers, but thus far have yielded little clinical benefit in PDAC. Based on re...

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Autores principales: Harper, Megan M., Lin, Miranda, Cavnar, Michael J., Pandalai, Prakash K., Patel, Reema A., Gao, Mei, Kim, Joseph
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262213/
https://www.ncbi.nlm.nih.gov/pubmed/35797269
http://dx.doi.org/10.1371/journal.pone.0270832
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author Harper, Megan M.
Lin, Miranda
Cavnar, Michael J.
Pandalai, Prakash K.
Patel, Reema A.
Gao, Mei
Kim, Joseph
author_facet Harper, Megan M.
Lin, Miranda
Cavnar, Michael J.
Pandalai, Prakash K.
Patel, Reema A.
Gao, Mei
Kim, Joseph
author_sort Harper, Megan M.
collection PubMed
description Despite recent therapeutic advances, pancreatic ductal adenocarcinoma (PDAC) remains a devastating disease with limited therapeutic options. Immune checkpoint inhibitors (ICIs) have demonstrated promising results in many cancers, but thus far have yielded little clinical benefit in PDAC. Based on recent combined targeting of programmed cell death protein-1 (PD-1) and C-X-C chemokine receptor 4 (CXCR4) in patient-derived xenografts (PDXs) and a pilot clinical trial, we sought to elucidate potential interactions between PD-1 and CXCR4. We observed concomitant expression and direct interaction of PD-1 and CXCR4 in PDAC cells. This interaction was disrupted upon CXCR4 antagonism with AMD3100 and led to increased cell surface expression of PD-1. Importantly, CXCR4-mediated PDAC cell migration was also blocked by PD-1 inhibition. Our work provides a possible mechanism by which prior studies have demonstrated that combined CXCR4 and PD-1 inhibition leads to decreased tumor growth. This is the first report investigating PD-1 and CXCR4 interactions in PDAC cells and our results can serve as the basis for further investigation of combined therapeutic targeting of CXCR4 and PD-1.
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spelling pubmed-92622132022-07-08 Interaction of immune checkpoint PD-1 and chemokine receptor 4 (CXCR4) promotes a malignant phenotype in pancreatic cancer cells Harper, Megan M. Lin, Miranda Cavnar, Michael J. Pandalai, Prakash K. Patel, Reema A. Gao, Mei Kim, Joseph PLoS One Research Article Despite recent therapeutic advances, pancreatic ductal adenocarcinoma (PDAC) remains a devastating disease with limited therapeutic options. Immune checkpoint inhibitors (ICIs) have demonstrated promising results in many cancers, but thus far have yielded little clinical benefit in PDAC. Based on recent combined targeting of programmed cell death protein-1 (PD-1) and C-X-C chemokine receptor 4 (CXCR4) in patient-derived xenografts (PDXs) and a pilot clinical trial, we sought to elucidate potential interactions between PD-1 and CXCR4. We observed concomitant expression and direct interaction of PD-1 and CXCR4 in PDAC cells. This interaction was disrupted upon CXCR4 antagonism with AMD3100 and led to increased cell surface expression of PD-1. Importantly, CXCR4-mediated PDAC cell migration was also blocked by PD-1 inhibition. Our work provides a possible mechanism by which prior studies have demonstrated that combined CXCR4 and PD-1 inhibition leads to decreased tumor growth. This is the first report investigating PD-1 and CXCR4 interactions in PDAC cells and our results can serve as the basis for further investigation of combined therapeutic targeting of CXCR4 and PD-1. Public Library of Science 2022-07-07 /pmc/articles/PMC9262213/ /pubmed/35797269 http://dx.doi.org/10.1371/journal.pone.0270832 Text en © 2022 Harper et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Harper, Megan M.
Lin, Miranda
Cavnar, Michael J.
Pandalai, Prakash K.
Patel, Reema A.
Gao, Mei
Kim, Joseph
Interaction of immune checkpoint PD-1 and chemokine receptor 4 (CXCR4) promotes a malignant phenotype in pancreatic cancer cells
title Interaction of immune checkpoint PD-1 and chemokine receptor 4 (CXCR4) promotes a malignant phenotype in pancreatic cancer cells
title_full Interaction of immune checkpoint PD-1 and chemokine receptor 4 (CXCR4) promotes a malignant phenotype in pancreatic cancer cells
title_fullStr Interaction of immune checkpoint PD-1 and chemokine receptor 4 (CXCR4) promotes a malignant phenotype in pancreatic cancer cells
title_full_unstemmed Interaction of immune checkpoint PD-1 and chemokine receptor 4 (CXCR4) promotes a malignant phenotype in pancreatic cancer cells
title_short Interaction of immune checkpoint PD-1 and chemokine receptor 4 (CXCR4) promotes a malignant phenotype in pancreatic cancer cells
title_sort interaction of immune checkpoint pd-1 and chemokine receptor 4 (cxcr4) promotes a malignant phenotype in pancreatic cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262213/
https://www.ncbi.nlm.nih.gov/pubmed/35797269
http://dx.doi.org/10.1371/journal.pone.0270832
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