Format

Send to

Choose Destination
Sci Rep. 2016 Aug 19;6:31745. doi: 10.1038/srep31745.

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

Lizotte PH1,2, Jones RE1,2, Keogh L1,2, Ivanova E1,2, Liu H1,2, Awad MM2,3,4, Hammerman PS2,3,4, Gill RR2,5, Richards WG4,6,7, Barbie DA2,4, Bass AJ2,4, Bueno R4,6,7, English JM1,2, Bittinger M1,2, Wong KK1,2,3,4.

Author information

1
Belfer Center for Applied Cancer Science, 360 Longwood Ave. Boston, MA 02115, USA.
2
Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02115, USA.
3
Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02115, USA.
4
Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA.
5
Department of Radiology, Brigham and Women's Hospital, 75 Francis St. Boston, MA 02115, USA.
6
Division of Thoracic Surgery, Brigham and Women's Hospital, 75 Francis St. Boston, MA 02115, USA.
7
International Mesothelioma Program of the Lung Center Surgery at Brigham and Women's Hospital, 75 Francis St. Boston, MA 02115, USA.

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.

PMID:
27539742
PMCID:
PMC4990967
DOI:
10.1038/srep31745
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center