Fine needle aspirate flow cytometric phenotyping characterizes immunosuppressive nature of the mesothelioma microenvironment

With the emergence of checkpoint blockade and other immunotherapeutic drugs, and the growing adoption of smaller, more flexible adaptive clinical trial designs, there is an unmet need to develop diagnostics that can rapidly immunophenotype patient tumors. The ability to longitudinally profile the tu...

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Main Authors:	Lizotte, Patrick H., Jones, Robert E., Keogh, Lauren, Ivanova, Elena, Liu, Hongye, Awad, Mark M., Hammerman, Peter S., Gill, Ritu R., Richards, William G., Barbie, David A., Bass, Adam J., Bueno, Raphael, English, Jessie M., Bittinger, Mark, Wong, Kwok-Kin
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990967/

id	pubmed-4990967
recordtype	oai_dc
spelling	pubmed-49909672016-08-30 Fine needle aspirate flow cytometric phenotyping characterizes immunosuppressive nature of the mesothelioma microenvironment Lizotte, Patrick H. Jones, Robert E. Keogh, Lauren Ivanova, Elena Liu, Hongye Awad, Mark M. Hammerman, Peter S. Gill, Ritu R. Richards, William G. Barbie, David A. Bass, Adam J. Bueno, Raphael English, Jessie M. Bittinger, Mark Wong, Kwok-Kin Article With the emergence of checkpoint blockade and other immunotherapeutic drugs, and the growing adoption of smaller, more flexible adaptive clinical trial designs, there is an unmet need to develop diagnostics that can rapidly immunophenotype patient tumors. The ability to longitudinally profile the tumor immune infiltrate in response to immunotherapy also presents a window of opportunity to illuminate mechanisms of resistance. We have developed a fine needle aspirate biopsy (FNA) platform to perform immune profiling on thoracic malignancies. Matching peripheral blood, bulk resected tumor, and FNA were analyzed from 13 mesothelioma patients. FNA samples yielded greater numbers of viable cells when compared to core needle biopsies. Cell numbers were adequate to perform flow cytometric analyses on T cell lineage, T cell activation and inhibitory receptor expression, and myeloid immunosuppressive checkpoint markers. FNA samples were representative of the tumor as a whole as assessed by head-to-head comparison to single cell suspensions of dissociated whole tumor. Parallel analysis of matched patient blood enabled us to establish quality assurance criteria to determine the accuracy of FNA procedures to sample tumor tissue. FNA biopsies provide a diagnostic to rapidly phenotype the tumor immune microenvironment that may be of great relevance to clinical trials. Nature Publishing Group 2016-08-19 /pmc/articles/PMC4990967/ /pubmed/27539742 http://dx.doi.org/10.1038/srep31745 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Lizotte, Patrick H. Jones, Robert E. Keogh, Lauren Ivanova, Elena Liu, Hongye Awad, Mark M. Hammerman, Peter S. Gill, Ritu R. Richards, William G. Barbie, David A. Bass, Adam J. Bueno, Raphael English, Jessie M. Bittinger, Mark Wong, Kwok-Kin
spellingShingle	Lizotte, Patrick H. Jones, Robert E. Keogh, Lauren Ivanova, Elena Liu, Hongye Awad, Mark M. Hammerman, Peter S. Gill, Ritu R. Richards, William G. Barbie, David A. Bass, Adam J. Bueno, Raphael English, Jessie M. Bittinger, Mark Wong, Kwok-Kin Fine needle aspirate flow cytometric phenotyping characterizes immunosuppressive nature of the mesothelioma microenvironment
author_facet	Lizotte, Patrick H. Jones, Robert E. Keogh, Lauren Ivanova, Elena Liu, Hongye Awad, Mark M. Hammerman, Peter S. Gill, Ritu R. Richards, William G. Barbie, David A. Bass, Adam J. Bueno, Raphael English, Jessie M. Bittinger, Mark Wong, Kwok-Kin
author_sort	Lizotte, Patrick H.
title	Fine needle aspirate flow cytometric phenotyping characterizes immunosuppressive nature of the mesothelioma microenvironment
title_short	Fine needle aspirate flow cytometric phenotyping characterizes immunosuppressive nature of the mesothelioma microenvironment
title_full	Fine needle aspirate flow cytometric phenotyping characterizes immunosuppressive nature of the mesothelioma microenvironment
title_fullStr	Fine needle aspirate flow cytometric phenotyping characterizes immunosuppressive nature of the mesothelioma microenvironment
title_full_unstemmed	Fine needle aspirate flow cytometric phenotyping characterizes immunosuppressive nature of the mesothelioma microenvironment
title_sort	fine needle aspirate flow cytometric phenotyping characterizes immunosuppressive nature of the mesothelioma microenvironment
description	With the emergence of checkpoint blockade and other immunotherapeutic drugs, and the growing adoption of smaller, more flexible adaptive clinical trial designs, there is an unmet need to develop diagnostics that can rapidly immunophenotype patient tumors. The ability to longitudinally profile the tumor immune infiltrate in response to immunotherapy also presents a window of opportunity to illuminate mechanisms of resistance. We have developed a fine needle aspirate biopsy (FNA) platform to perform immune profiling on thoracic malignancies. Matching peripheral blood, bulk resected tumor, and FNA were analyzed from 13 mesothelioma patients. FNA samples yielded greater numbers of viable cells when compared to core needle biopsies. Cell numbers were adequate to perform flow cytometric analyses on T cell lineage, T cell activation and inhibitory receptor expression, and myeloid immunosuppressive checkpoint markers. FNA samples were representative of the tumor as a whole as assessed by head-to-head comparison to single cell suspensions of dissociated whole tumor. Parallel analysis of matched patient blood enabled us to establish quality assurance criteria to determine the accuracy of FNA procedures to sample tumor tissue. FNA biopsies provide a diagnostic to rapidly phenotype the tumor immune microenvironment that may be of great relevance to clinical trials.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990967/
_version_	1613630500905156608

Fine needle aspirate flow cytometric phenotyping characterizes immunosuppressive nature of the mesothelioma microenvironment

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