Expression of Programmed Cell Death Ligand 1 and Associated Lymphocyte Infiltration in Olfactory Neuroblastoma

Nyall R. London, Lisa M. Rooper, Justin A. Bishop, Haiying Xu, Lydia J. Bernhardt, Masaru Ishii, Christine L. Hann, Janis M. Taube, Evgeny Izumchenko, Daria A. Gaykalova, Gary L. Gallia

Research output: Contribution to journalArticle

Abstract

Background: Programmed cell death ligand 1 (PD-L1) is a transmembrane glycoprotein that interacts with the receptor programmed cell death 1 (PD-1) to suppress T-cell activation, reduce adjacent tissue damage, and promote tolerance to self-antigens. Tumors may express PD-L1 as a mechanism to evade immune detection. Recent clinical trials have demonstrated the efficacy of PD-L1/PD-1 antagonists through activation of tumor-infiltrated CD8+ T cells. The aim of this study was to determine the expression pattern of PD-L1 and PD-1 in olfactory neuroblastoma (ONB) tumor cells and to determine the presence of PD-1+ and CD8+ lymphocytes in the ONB immune microenvironment. Methods: Immunohistochemistry for expression of PD-L1, PD-1, and CD8 was performed on paraffin-embedded ONB tissue. Results: Of the 10 primary site ONB samples, 4 demonstrated positive PD-L1 expression. Of PD-L1+ tumors, the 2 highest expressing samples were found to contain PD-1+ tumor cells. Of the 4 available metastatic samples, all of which arose from PD-L1 primary site ONB, 3 were positive for PD-L1 and contained PD-1+ tumor cells. PD-L1+ primary and metastatic tumors also demonstrated increased PD-1+ infiltrating lymphocytes in the tumor and stroma (11.6- and 4.62-fold increase) compared with PD-L1 samples (P < 0.05 and P = 0.068 respectively). PD-L1+ specimens demonstrated increased CD8+ lymphocytes in the tumor and stroma (7.46- and 2.14-fold increase) compared with PD-L1 tumors (P < 0.05 for both). Conclusions: These data demonstrate that a proportion of ONB primary and metastatic tumors express PD-L1 and possess an associated tumor and stromal infiltrate of PD-1+ and CD8+ lymphocytes.

Original languageEnglish (US)
JournalWorld neurosurgery
DOIs
StateAccepted/In press - Jan 1 2020

Fingerprint

Olfactory Esthesioneuroblastoma
Cell Death
Lymphocytes
Ligands
CD274 Antigen
Neoplasms
Programmed Cell Death 1 Receptor
T-Lymphocytes
Tumor-Infiltrating Lymphocytes

Keywords

  • Esthesioneuroblastoma
  • Immune checkpoint inhibitors
  • Immunotherapy
  • Olfactory neuroblastoma
  • PD-L1

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Cite this

Expression of Programmed Cell Death Ligand 1 and Associated Lymphocyte Infiltration in Olfactory Neuroblastoma. / London, Nyall R.; Rooper, Lisa M.; Bishop, Justin A.; Xu, Haiying; Bernhardt, Lydia J.; Ishii, Masaru; Hann, Christine L.; Taube, Janis M.; Izumchenko, Evgeny; Gaykalova, Daria A.; Gallia, Gary L.

In: World neurosurgery, 01.01.2020.

Research output: Contribution to journalArticle

London, Nyall R. ; Rooper, Lisa M. ; Bishop, Justin A. ; Xu, Haiying ; Bernhardt, Lydia J. ; Ishii, Masaru ; Hann, Christine L. ; Taube, Janis M. ; Izumchenko, Evgeny ; Gaykalova, Daria A. ; Gallia, Gary L. / Expression of Programmed Cell Death Ligand 1 and Associated Lymphocyte Infiltration in Olfactory Neuroblastoma. In: World neurosurgery. 2020.
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abstract = "Background: Programmed cell death ligand 1 (PD-L1) is a transmembrane glycoprotein that interacts with the receptor programmed cell death 1 (PD-1) to suppress T-cell activation, reduce adjacent tissue damage, and promote tolerance to self-antigens. Tumors may express PD-L1 as a mechanism to evade immune detection. Recent clinical trials have demonstrated the efficacy of PD-L1/PD-1 antagonists through activation of tumor-infiltrated CD8+ T cells. The aim of this study was to determine the expression pattern of PD-L1 and PD-1 in olfactory neuroblastoma (ONB) tumor cells and to determine the presence of PD-1+ and CD8+ lymphocytes in the ONB immune microenvironment. Methods: Immunohistochemistry for expression of PD-L1, PD-1, and CD8 was performed on paraffin-embedded ONB tissue. Results: Of the 10 primary site ONB samples, 4 demonstrated positive PD-L1 expression. Of PD-L1+ tumors, the 2 highest expressing samples were found to contain PD-1+ tumor cells. Of the 4 available metastatic samples, all of which arose from PD-L1− primary site ONB, 3 were positive for PD-L1 and contained PD-1+ tumor cells. PD-L1+ primary and metastatic tumors also demonstrated increased PD-1+ infiltrating lymphocytes in the tumor and stroma (11.6- and 4.62-fold increase) compared with PD-L1− samples (P < 0.05 and P = 0.068 respectively). PD-L1+ specimens demonstrated increased CD8+ lymphocytes in the tumor and stroma (7.46- and 2.14-fold increase) compared with PD-L1− tumors (P < 0.05 for both). Conclusions: These data demonstrate that a proportion of ONB primary and metastatic tumors express PD-L1 and possess an associated tumor and stromal infiltrate of PD-1+ and CD8+ lymphocytes.",
keywords = "Esthesioneuroblastoma, Immune checkpoint inhibitors, Immunotherapy, Olfactory neuroblastoma, PD-L1",
author = "London, {Nyall R.} and Rooper, {Lisa M.} and Bishop, {Justin A.} and Haiying Xu and Bernhardt, {Lydia J.} and Masaru Ishii and Hann, {Christine L.} and Taube, {Janis M.} and Evgeny Izumchenko and Gaykalova, {Daria A.} and Gallia, {Gary L.}",
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T1 - Expression of Programmed Cell Death Ligand 1 and Associated Lymphocyte Infiltration in Olfactory Neuroblastoma

AU - London, Nyall R.

AU - Rooper, Lisa M.

AU - Bishop, Justin A.

AU - Xu, Haiying

AU - Bernhardt, Lydia J.

AU - Ishii, Masaru

AU - Hann, Christine L.

AU - Taube, Janis M.

AU - Izumchenko, Evgeny

AU - Gaykalova, Daria A.

AU - Gallia, Gary L.

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Background: Programmed cell death ligand 1 (PD-L1) is a transmembrane glycoprotein that interacts with the receptor programmed cell death 1 (PD-1) to suppress T-cell activation, reduce adjacent tissue damage, and promote tolerance to self-antigens. Tumors may express PD-L1 as a mechanism to evade immune detection. Recent clinical trials have demonstrated the efficacy of PD-L1/PD-1 antagonists through activation of tumor-infiltrated CD8+ T cells. The aim of this study was to determine the expression pattern of PD-L1 and PD-1 in olfactory neuroblastoma (ONB) tumor cells and to determine the presence of PD-1+ and CD8+ lymphocytes in the ONB immune microenvironment. Methods: Immunohistochemistry for expression of PD-L1, PD-1, and CD8 was performed on paraffin-embedded ONB tissue. Results: Of the 10 primary site ONB samples, 4 demonstrated positive PD-L1 expression. Of PD-L1+ tumors, the 2 highest expressing samples were found to contain PD-1+ tumor cells. Of the 4 available metastatic samples, all of which arose from PD-L1− primary site ONB, 3 were positive for PD-L1 and contained PD-1+ tumor cells. PD-L1+ primary and metastatic tumors also demonstrated increased PD-1+ infiltrating lymphocytes in the tumor and stroma (11.6- and 4.62-fold increase) compared with PD-L1− samples (P < 0.05 and P = 0.068 respectively). PD-L1+ specimens demonstrated increased CD8+ lymphocytes in the tumor and stroma (7.46- and 2.14-fold increase) compared with PD-L1− tumors (P < 0.05 for both). Conclusions: These data demonstrate that a proportion of ONB primary and metastatic tumors express PD-L1 and possess an associated tumor and stromal infiltrate of PD-1+ and CD8+ lymphocytes.

AB - Background: Programmed cell death ligand 1 (PD-L1) is a transmembrane glycoprotein that interacts with the receptor programmed cell death 1 (PD-1) to suppress T-cell activation, reduce adjacent tissue damage, and promote tolerance to self-antigens. Tumors may express PD-L1 as a mechanism to evade immune detection. Recent clinical trials have demonstrated the efficacy of PD-L1/PD-1 antagonists through activation of tumor-infiltrated CD8+ T cells. The aim of this study was to determine the expression pattern of PD-L1 and PD-1 in olfactory neuroblastoma (ONB) tumor cells and to determine the presence of PD-1+ and CD8+ lymphocytes in the ONB immune microenvironment. Methods: Immunohistochemistry for expression of PD-L1, PD-1, and CD8 was performed on paraffin-embedded ONB tissue. Results: Of the 10 primary site ONB samples, 4 demonstrated positive PD-L1 expression. Of PD-L1+ tumors, the 2 highest expressing samples were found to contain PD-1+ tumor cells. Of the 4 available metastatic samples, all of which arose from PD-L1− primary site ONB, 3 were positive for PD-L1 and contained PD-1+ tumor cells. PD-L1+ primary and metastatic tumors also demonstrated increased PD-1+ infiltrating lymphocytes in the tumor and stroma (11.6- and 4.62-fold increase) compared with PD-L1− samples (P < 0.05 and P = 0.068 respectively). PD-L1+ specimens demonstrated increased CD8+ lymphocytes in the tumor and stroma (7.46- and 2.14-fold increase) compared with PD-L1− tumors (P < 0.05 for both). Conclusions: These data demonstrate that a proportion of ONB primary and metastatic tumors express PD-L1 and possess an associated tumor and stromal infiltrate of PD-1+ and CD8+ lymphocytes.

KW - Esthesioneuroblastoma

KW - Immune checkpoint inhibitors

KW - Immunotherapy

KW - Olfactory neuroblastoma

KW - PD-L1

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