Characterization of the Neuroendocrine Tumor Immune Microenvironment

Annacarolina Da Silva, Michaela Bowden, Sui Zhang, Yohei Masugi, Aaron R. Thorner, Zachary T. Herbert, Chensheng Willa Zhou, Lauren Brais, Jennifer A. Chan, F. Stephen Hodi, Scott Rodig, Shuji Ogino, Matthew H. Kulke

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Objectives The immune environment and the potential for neuroendocrine tumors (NETs) to respond to immune checkpoint inhibitors remain largely unexplored. We assessed immune checkpoint marker expression, lymphocytic infiltrate, and associated mutational profiles in a cohort of small intestine and pancreatic NETs. Methods We assessed expression of PDCD1 (PD-1), CD274 (PD-L1), and PDCD1LG2 (PD-L2) in archival tissue from 64 small intestine (SINETs) and 31 pancreatic NETs (pNET). We additionally assessed T-cell infiltrates, categorizing T-cell subsets based on expression of the T-cell markers CD3, CD8, CD45RO (PTPRC), or FOXP3. Finally, we explored associations between immune checkpoint marker expression, lymphocytic infiltrate, and tumor mutational profiles. Results Expression of PD-1 or PD-L1 in small intestine or pancreatic NET was rare, whereas expression of PD-L2 was common in both NET subtypes. T-cell infiltrates were more abundant in pNET than in SINET. We found no clear associations between immune checkpoint marker expression, immune infiltrates, and specific mutational profile within each tumor type. Conclusions Our findings provide an initial assessment of the immune environment of well-differentiated NETs. Further studies to define the immunologic differences between pNET and SINET, as well as the role of PD-L2 in these tumors, are warranted.

Original languageEnglish
Pages (from-to)1123-1129
Number of pages7
JournalPancreas
Volume47
Issue number9
DOIs
Publication statusPublished - 2018 Oct 1
Externally publishedYes

Fingerprint

Tumor Microenvironment
Neuroendocrine Tumors
Small Intestine
Biomarkers
T-Lymphocytes
Neoplasms
T-Lymphocyte Subsets

Keywords

  • immune checkpoint
  • neuroendocrine tumor
  • PD-1
  • PD-L1
  • PD-L2
  • T-cell markers

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

Cite this

Da Silva, A., Bowden, M., Zhang, S., Masugi, Y., Thorner, A. R., Herbert, Z. T., ... Kulke, M. H. (2018). Characterization of the Neuroendocrine Tumor Immune Microenvironment. Pancreas, 47(9), 1123-1129. https://doi.org/10.1097/MPA.0000000000001150

Characterization of the Neuroendocrine Tumor Immune Microenvironment. / Da Silva, Annacarolina; Bowden, Michaela; Zhang, Sui; Masugi, Yohei; Thorner, Aaron R.; Herbert, Zachary T.; Zhou, Chensheng Willa; Brais, Lauren; Chan, Jennifer A.; Hodi, F. Stephen; Rodig, Scott; Ogino, Shuji; Kulke, Matthew H.

In: Pancreas, Vol. 47, No. 9, 01.10.2018, p. 1123-1129.

Research output: Contribution to journalArticle

Da Silva, A, Bowden, M, Zhang, S, Masugi, Y, Thorner, AR, Herbert, ZT, Zhou, CW, Brais, L, Chan, JA, Hodi, FS, Rodig, S, Ogino, S & Kulke, MH 2018, 'Characterization of the Neuroendocrine Tumor Immune Microenvironment', Pancreas, vol. 47, no. 9, pp. 1123-1129. https://doi.org/10.1097/MPA.0000000000001150
Da Silva A, Bowden M, Zhang S, Masugi Y, Thorner AR, Herbert ZT et al. Characterization of the Neuroendocrine Tumor Immune Microenvironment. Pancreas. 2018 Oct 1;47(9):1123-1129. https://doi.org/10.1097/MPA.0000000000001150
Da Silva, Annacarolina ; Bowden, Michaela ; Zhang, Sui ; Masugi, Yohei ; Thorner, Aaron R. ; Herbert, Zachary T. ; Zhou, Chensheng Willa ; Brais, Lauren ; Chan, Jennifer A. ; Hodi, F. Stephen ; Rodig, Scott ; Ogino, Shuji ; Kulke, Matthew H. / Characterization of the Neuroendocrine Tumor Immune Microenvironment. In: Pancreas. 2018 ; Vol. 47, No. 9. pp. 1123-1129.
@article{3bb0e6e465cf4c979d6ae17a8fec08d7,
title = "Characterization of the Neuroendocrine Tumor Immune Microenvironment",
abstract = "Objectives The immune environment and the potential for neuroendocrine tumors (NETs) to respond to immune checkpoint inhibitors remain largely unexplored. We assessed immune checkpoint marker expression, lymphocytic infiltrate, and associated mutational profiles in a cohort of small intestine and pancreatic NETs. Methods We assessed expression of PDCD1 (PD-1), CD274 (PD-L1), and PDCD1LG2 (PD-L2) in archival tissue from 64 small intestine (SINETs) and 31 pancreatic NETs (pNET). We additionally assessed T-cell infiltrates, categorizing T-cell subsets based on expression of the T-cell markers CD3, CD8, CD45RO (PTPRC), or FOXP3. Finally, we explored associations between immune checkpoint marker expression, lymphocytic infiltrate, and tumor mutational profiles. Results Expression of PD-1 or PD-L1 in small intestine or pancreatic NET was rare, whereas expression of PD-L2 was common in both NET subtypes. T-cell infiltrates were more abundant in pNET than in SINET. We found no clear associations between immune checkpoint marker expression, immune infiltrates, and specific mutational profile within each tumor type. Conclusions Our findings provide an initial assessment of the immune environment of well-differentiated NETs. Further studies to define the immunologic differences between pNET and SINET, as well as the role of PD-L2 in these tumors, are warranted.",
keywords = "immune checkpoint, neuroendocrine tumor, PD-1, PD-L1, PD-L2, T-cell markers",
author = "{Da Silva}, Annacarolina and Michaela Bowden and Sui Zhang and Yohei Masugi and Thorner, {Aaron R.} and Herbert, {Zachary T.} and Zhou, {Chensheng Willa} and Lauren Brais and Chan, {Jennifer A.} and Hodi, {F. Stephen} and Scott Rodig and Shuji Ogino and Kulke, {Matthew H.}",
year = "2018",
month = "10",
day = "1",
doi = "10.1097/MPA.0000000000001150",
language = "English",
volume = "47",
pages = "1123--1129",
journal = "Pancreas",
issn = "0885-3177",
publisher = "Lippincott Williams and Wilkins",
number = "9",

}

TY - JOUR

T1 - Characterization of the Neuroendocrine Tumor Immune Microenvironment

AU - Da Silva, Annacarolina

AU - Bowden, Michaela

AU - Zhang, Sui

AU - Masugi, Yohei

AU - Thorner, Aaron R.

AU - Herbert, Zachary T.

AU - Zhou, Chensheng Willa

AU - Brais, Lauren

AU - Chan, Jennifer A.

AU - Hodi, F. Stephen

AU - Rodig, Scott

AU - Ogino, Shuji

AU - Kulke, Matthew H.

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Objectives The immune environment and the potential for neuroendocrine tumors (NETs) to respond to immune checkpoint inhibitors remain largely unexplored. We assessed immune checkpoint marker expression, lymphocytic infiltrate, and associated mutational profiles in a cohort of small intestine and pancreatic NETs. Methods We assessed expression of PDCD1 (PD-1), CD274 (PD-L1), and PDCD1LG2 (PD-L2) in archival tissue from 64 small intestine (SINETs) and 31 pancreatic NETs (pNET). We additionally assessed T-cell infiltrates, categorizing T-cell subsets based on expression of the T-cell markers CD3, CD8, CD45RO (PTPRC), or FOXP3. Finally, we explored associations between immune checkpoint marker expression, lymphocytic infiltrate, and tumor mutational profiles. Results Expression of PD-1 or PD-L1 in small intestine or pancreatic NET was rare, whereas expression of PD-L2 was common in both NET subtypes. T-cell infiltrates were more abundant in pNET than in SINET. We found no clear associations between immune checkpoint marker expression, immune infiltrates, and specific mutational profile within each tumor type. Conclusions Our findings provide an initial assessment of the immune environment of well-differentiated NETs. Further studies to define the immunologic differences between pNET and SINET, as well as the role of PD-L2 in these tumors, are warranted.

AB - Objectives The immune environment and the potential for neuroendocrine tumors (NETs) to respond to immune checkpoint inhibitors remain largely unexplored. We assessed immune checkpoint marker expression, lymphocytic infiltrate, and associated mutational profiles in a cohort of small intestine and pancreatic NETs. Methods We assessed expression of PDCD1 (PD-1), CD274 (PD-L1), and PDCD1LG2 (PD-L2) in archival tissue from 64 small intestine (SINETs) and 31 pancreatic NETs (pNET). We additionally assessed T-cell infiltrates, categorizing T-cell subsets based on expression of the T-cell markers CD3, CD8, CD45RO (PTPRC), or FOXP3. Finally, we explored associations between immune checkpoint marker expression, lymphocytic infiltrate, and tumor mutational profiles. Results Expression of PD-1 or PD-L1 in small intestine or pancreatic NET was rare, whereas expression of PD-L2 was common in both NET subtypes. T-cell infiltrates were more abundant in pNET than in SINET. We found no clear associations between immune checkpoint marker expression, immune infiltrates, and specific mutational profile within each tumor type. Conclusions Our findings provide an initial assessment of the immune environment of well-differentiated NETs. Further studies to define the immunologic differences between pNET and SINET, as well as the role of PD-L2 in these tumors, are warranted.

KW - immune checkpoint

KW - neuroendocrine tumor

KW - PD-1

KW - PD-L1

KW - PD-L2

KW - T-cell markers

UR - http://www.scopus.com/inward/record.url?scp=85053687219&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053687219&partnerID=8YFLogxK

U2 - 10.1097/MPA.0000000000001150

DO - 10.1097/MPA.0000000000001150

M3 - Article

C2 - 30153220

AN - SCOPUS:85053687219

VL - 47

SP - 1123

EP - 1129

JO - Pancreas

JF - Pancreas

SN - 0885-3177

IS - 9

ER -