title: Fine needle aspirate flow cytometric phenotyping characterizes immunosuppressive nature of the mesothelioma microenvironment.
abstract: 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.
authors.affiliation: Belfer Center for Applied Cancer Science, 360 Longwood Ave. Boston, MA 02115, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02115, USA.
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Lizotte
authors.affiliation: Belfer Center for Applied Cancer Science, 360 Longwood Ave. Boston, MA 02115, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02115, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Jones
authors.affiliation: Belfer Center for Applied Cancer Science, 360 Longwood Ave. Boston, MA 02115, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02115, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Keogh
authors.affiliation: Belfer Center for Applied Cancer Science, 360 Longwood Ave. Boston, MA 02115, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02115, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Ivanova
authors.affiliation: Belfer Center for Applied Cancer Science, 360 Longwood Ave. Boston, MA 02115, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02115, USA.
authors.forename: Hongye
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02115, USA.|Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02115, USA.|Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Awad
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02115, USA.|Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02115, USA.|Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Hammerman
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02115, USA.|Department of Radiology, Brigham and Women's Hospital, 75 Francis St. Boston, MA 02115, USA.
authors.forename: Ritu R
authors.initials: RR
authors.lastname: Gill
authors.affiliation: Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA.|Division of Thoracic Surgery, Brigham and Women's Hospital, 75 Francis St. Boston, MA 02115, USA.|International Mesothelioma Program of the Lung Center Surgery at Brigham and Women's Hospital, 75 Francis St. Boston, MA 02115, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Richards
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02115, USA.|Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Barbie
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02115, USA.|Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Bass
authors.affiliation: Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA.|Division of Thoracic Surgery, Brigham and Women's Hospital, 75 Francis St. Boston, MA 02115, USA.|International Mesothelioma Program of the Lung Center Surgery at Brigham and Women's Hospital, 75 Francis St. Boston, MA 02115, USA.
authors.forename: Raphael
authors.initials: R
authors.lastname: Bueno
authors.affiliation: Belfer Center for Applied Cancer Science, 360 Longwood Ave. Boston, MA 02115, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02115, USA.
authors.forename: Jessie M
authors.initials: JM
authors.lastname: English
authors.affiliation: Belfer Center for Applied Cancer Science, 360 Longwood Ave. Boston, MA 02115, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02115, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Bittinger
authors.affiliation: Belfer Center for Applied Cancer Science, 360 Longwood Ave. Boston, MA 02115, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02115, USA.|Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02115, USA.|Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA.
authors.forename: Kwok-Kin
authors.initials: KK
authors.lastname: Wong
mesh_terms: D044963:Biopsy, Fine-Needle; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007108:Immune Tolerance; D008297:Male; D008654:Mesothelioma / Q000175:diagnosis / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D013899:Thoracic Neoplasms / Q000175:diagnosis / Q000276:immunology / Q000473:pathology; D059016:Tumor Microenvironment / Q000276:immunology*