Therapeutic targeting of regulatory T cells enhances tumor-specific CD8+ T cell responses in Epstein-Barr virus associated nasopharyngeal carcinoma

Mark Fogg; John R. Murphy; Jochen Lorch; Marshall Posner; Fred Wang

doi:10.1016/j.virol.2013.03.016

Therapeutic targeting of regulatory T cells enhances tumor-specific CD8+ T cell responses in Epstein-Barr virus associated nasopharyngeal carcinoma

Mark Fogg, John R. Murphy, Jochen Lorch, Marshall Posner, Fred Wang^*

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

Epstein-Barr virus (EBV) is associated with multiple malignancies including nasopharyngeal carcinoma (NPC). In nasopharynx cancer, CD8+ T cells specific for EBV Nuclear Antigen-1 (EBNA-1) and Latent Membrane Protein 2 (LMP2) are important components of anti-tumor immunity since both are consistently expressed in NPC. We have previously shown that EBNA-1-specific CD8+ T cell responses were suppressed in NPC patients compared to healthy controls. We now find that CD8+ T cell responses specific for LMP2 are also abnormal in NPC patients, and both EBNA-1- and LMP2-specific responses are suppressed by regulatory T cells (Treg). EBNA-1 and LMP2-specific CD8+ T cell responses, as well as immune control of EBV-infected cells in vitro, could be restored by the depletion of Tregs and by use of a clinically approved drug targeting Tregs. Thus, in vivo modulation of Tregs may be an effective means of enhancing these anti-tumor immune responses in NPC patients.

Original language	English (US)
Pages (from-to)	107-113
Number of pages	7
Journal	Virology
Volume	441
Issue number	2
DOIs	https://doi.org/10.1016/j.virol.2013.03.016
State	Published - Jul 5 2013

Funding

This work was supported by Grants from the Dana Farber Cancer Institute Friends of Head and Neck Cancer Research and the National Institutes of Health ( CA68051 , CA132279 ). We thank the Head and Neck Clinical Research Team at the DFCI for managing clinical sample collection and all of the NPC patients and healthy donors who so generously contributed blood for these studies. Appendix A

Keywords

CD8+ T cells
Epstein-Barr virus
Nasopharyngeal carcinoma
Ontak
T regulatory cells

ASJC Scopus subject areas

Virology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.virol.2013.03.016

Cite this

@article{d4e7a5663f3f4a5aa6fda333bda6d2fd,

title = "Therapeutic targeting of regulatory T cells enhances tumor-specific CD8+ T cell responses in Epstein-Barr virus associated nasopharyngeal carcinoma",

abstract = "Epstein-Barr virus (EBV) is associated with multiple malignancies including nasopharyngeal carcinoma (NPC). In nasopharynx cancer, CD8+ T cells specific for EBV Nuclear Antigen-1 (EBNA-1) and Latent Membrane Protein 2 (LMP2) are important components of anti-tumor immunity since both are consistently expressed in NPC. We have previously shown that EBNA-1-specific CD8+ T cell responses were suppressed in NPC patients compared to healthy controls. We now find that CD8+ T cell responses specific for LMP2 are also abnormal in NPC patients, and both EBNA-1- and LMP2-specific responses are suppressed by regulatory T cells (Treg). EBNA-1 and LMP2-specific CD8+ T cell responses, as well as immune control of EBV-infected cells in vitro, could be restored by the depletion of Tregs and by use of a clinically approved drug targeting Tregs. Thus, in vivo modulation of Tregs may be an effective means of enhancing these anti-tumor immune responses in NPC patients.",

keywords = "CD8+ T cells, Epstein-Barr virus, Nasopharyngeal carcinoma, Ontak, T regulatory cells",

author = "Mark Fogg and Murphy, \{John R.\} and Jochen Lorch and Marshall Posner and Fred Wang",

note = "Funding Information: This work was supported by Grants from the Dana Farber Cancer Institute Friends of Head and Neck Cancer Research and the National Institutes of Health ( CA68051 , CA132279 ). We thank the Head and Neck Clinical Research Team at the DFCI for managing clinical sample collection and all of the NPC patients and healthy donors who so generously contributed blood for these studies. Appendix A ",

year = "2013",

month = jul,

day = "5",

doi = "10.1016/j.virol.2013.03.016",

language = "English (US)",

volume = "441",

pages = "107--113",

journal = "Virology",

issn = "0042-6822",

publisher = "Academic Press Inc.",

number = "2",

}

TY - JOUR

T1 - Therapeutic targeting of regulatory T cells enhances tumor-specific CD8+ T cell responses in Epstein-Barr virus associated nasopharyngeal carcinoma

AU - Fogg, Mark

AU - Murphy, John R.

AU - Lorch, Jochen

AU - Posner, Marshall

AU - Wang, Fred

N1 - Funding Information: This work was supported by Grants from the Dana Farber Cancer Institute Friends of Head and Neck Cancer Research and the National Institutes of Health ( CA68051 , CA132279 ). We thank the Head and Neck Clinical Research Team at the DFCI for managing clinical sample collection and all of the NPC patients and healthy donors who so generously contributed blood for these studies. Appendix A

PY - 2013/7/5

Y1 - 2013/7/5

N2 - Epstein-Barr virus (EBV) is associated with multiple malignancies including nasopharyngeal carcinoma (NPC). In nasopharynx cancer, CD8+ T cells specific for EBV Nuclear Antigen-1 (EBNA-1) and Latent Membrane Protein 2 (LMP2) are important components of anti-tumor immunity since both are consistently expressed in NPC. We have previously shown that EBNA-1-specific CD8+ T cell responses were suppressed in NPC patients compared to healthy controls. We now find that CD8+ T cell responses specific for LMP2 are also abnormal in NPC patients, and both EBNA-1- and LMP2-specific responses are suppressed by regulatory T cells (Treg). EBNA-1 and LMP2-specific CD8+ T cell responses, as well as immune control of EBV-infected cells in vitro, could be restored by the depletion of Tregs and by use of a clinically approved drug targeting Tregs. Thus, in vivo modulation of Tregs may be an effective means of enhancing these anti-tumor immune responses in NPC patients.

AB - Epstein-Barr virus (EBV) is associated with multiple malignancies including nasopharyngeal carcinoma (NPC). In nasopharynx cancer, CD8+ T cells specific for EBV Nuclear Antigen-1 (EBNA-1) and Latent Membrane Protein 2 (LMP2) are important components of anti-tumor immunity since both are consistently expressed in NPC. We have previously shown that EBNA-1-specific CD8+ T cell responses were suppressed in NPC patients compared to healthy controls. We now find that CD8+ T cell responses specific for LMP2 are also abnormal in NPC patients, and both EBNA-1- and LMP2-specific responses are suppressed by regulatory T cells (Treg). EBNA-1 and LMP2-specific CD8+ T cell responses, as well as immune control of EBV-infected cells in vitro, could be restored by the depletion of Tregs and by use of a clinically approved drug targeting Tregs. Thus, in vivo modulation of Tregs may be an effective means of enhancing these anti-tumor immune responses in NPC patients.

KW - CD8+ T cells

KW - Epstein-Barr virus

KW - Nasopharyngeal carcinoma

KW - Ontak

KW - T regulatory cells

UR - http://www.scopus.com/inward/record.url?scp=84877920105&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84877920105&partnerID=8YFLogxK

U2 - 10.1016/j.virol.2013.03.016

DO - 10.1016/j.virol.2013.03.016

M3 - Article

C2 - 23601786

AN - SCOPUS:84877920105

SN - 0042-6822

VL - 441

SP - 107

EP - 113

JO - Virology

JF - Virology

IS - 2

ER -

Therapeutic targeting of regulatory T cells enhances tumor-specific CD8+ T cell responses in Epstein-Barr virus associated nasopharyngeal carcinoma

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this