Expression of MHC I and NK ligands on human CD133+ glioma cells: possible targets of immunotherapy.

Anhua Wu, Steve Wiesner, Jing Xiao, Katya Ericson, Wei Chen, Walter A. Hall, Walter C. Low, John R. Ohlfest

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

Mounting evidence suggests that gliomas are comprised of differentiated tumor cells and brain tumor stem cells (BTSCs). BTSCs account for a fraction of total tumor cells, yet are apparently the sole cells capable of tumor initiation and tumor renewal. BTSCs have been identified as the CD133-positive fraction of human glioma, whereas their CD133-negative daughter cells have limited proliferative ability and are not tumorogenic. It is well established that the bulk tumor mass escapes immune surveillance by multiple mechanisms, yet little is known about the immunogenicity of the CD133-positive fraction of the tumor mass. We investigated the immunogenicity of CD133-positive cells in two human astrocytoma and two glioblastoma multiforme samples. Flow cytometry analyses revealed that the majority of CD133-positive cells do not express detectable MHC I or natural killer (NK) cell activating ligands, which may render them resistant to adaptive and innate immune surveillance. Incubating CD133-positive cells in interferon gamma (INF-gamma) significantly increased the percentage of CD133-positive cells that expressed MHC I and NK cell ligands. Furthermore, pretreatment of CD133-positive cells with INF-gamma rendered them sensitive to NK cell-mediated lysis in vitro. There were no consistent differences in immunogenicity between the CD133-positive and CD133-negative cells in these experiments. We conclude that CD133-posistive and CD133-negative glioma cells may be similarly resistant to immune surveillance, but that INF-gamma may partially restore their immunogenicity and potentiate their lysis by NK cells.

Original languageEnglish (US)
Pages (from-to)121-131
Number of pages11
JournalJournal of Neuro-Oncology
Volume83
Issue number2
DOIs
StatePublished - Jan 1 2007

Fingerprint

Glioma
Immunotherapy
Ligands
Natural Killer Cells
Interferon-gamma
Neoplastic Stem Cells
Brain Neoplasms
Neoplasms
Tumor Escape
Astrocytoma
Glioblastoma
Flow Cytometry

Cite this

Expression of MHC I and NK ligands on human CD133+ glioma cells : possible targets of immunotherapy. / Wu, Anhua; Wiesner, Steve; Xiao, Jing; Ericson, Katya; Chen, Wei; Hall, Walter A.; Low, Walter C.; Ohlfest, John R.

In: Journal of Neuro-Oncology, Vol. 83, No. 2, 01.01.2007, p. 121-131.

Research output: Contribution to journalArticle

Wu, Anhua ; Wiesner, Steve ; Xiao, Jing ; Ericson, Katya ; Chen, Wei ; Hall, Walter A. ; Low, Walter C. ; Ohlfest, John R. / Expression of MHC I and NK ligands on human CD133+ glioma cells : possible targets of immunotherapy. In: Journal of Neuro-Oncology. 2007 ; Vol. 83, No. 2. pp. 121-131.
@article{eee4e94919dd4a5eb3998eae531be80c,
title = "Expression of MHC I and NK ligands on human CD133+ glioma cells: possible targets of immunotherapy.",
abstract = "Mounting evidence suggests that gliomas are comprised of differentiated tumor cells and brain tumor stem cells (BTSCs). BTSCs account for a fraction of total tumor cells, yet are apparently the sole cells capable of tumor initiation and tumor renewal. BTSCs have been identified as the CD133-positive fraction of human glioma, whereas their CD133-negative daughter cells have limited proliferative ability and are not tumorogenic. It is well established that the bulk tumor mass escapes immune surveillance by multiple mechanisms, yet little is known about the immunogenicity of the CD133-positive fraction of the tumor mass. We investigated the immunogenicity of CD133-positive cells in two human astrocytoma and two glioblastoma multiforme samples. Flow cytometry analyses revealed that the majority of CD133-positive cells do not express detectable MHC I or natural killer (NK) cell activating ligands, which may render them resistant to adaptive and innate immune surveillance. Incubating CD133-positive cells in interferon gamma (INF-gamma) significantly increased the percentage of CD133-positive cells that expressed MHC I and NK cell ligands. Furthermore, pretreatment of CD133-positive cells with INF-gamma rendered them sensitive to NK cell-mediated lysis in vitro. There were no consistent differences in immunogenicity between the CD133-positive and CD133-negative cells in these experiments. We conclude that CD133-posistive and CD133-negative glioma cells may be similarly resistant to immune surveillance, but that INF-gamma may partially restore their immunogenicity and potentiate their lysis by NK cells.",
author = "Anhua Wu and Steve Wiesner and Jing Xiao and Katya Ericson and Wei Chen and Hall, {Walter A.} and Low, {Walter C.} and Ohlfest, {John R.}",
year = "2007",
month = "1",
day = "1",
doi = "10.1007/s11060-006-9265-3",
language = "English (US)",
volume = "83",
pages = "121--131",
journal = "Journal of Neuro-Oncology",
issn = "0167-594X",
publisher = "Kluwer Academic Publishers",
number = "2",

}

TY - JOUR

T1 - Expression of MHC I and NK ligands on human CD133+ glioma cells

T2 - possible targets of immunotherapy.

AU - Wu, Anhua

AU - Wiesner, Steve

AU - Xiao, Jing

AU - Ericson, Katya

AU - Chen, Wei

AU - Hall, Walter A.

AU - Low, Walter C.

AU - Ohlfest, John R.

PY - 2007/1/1

Y1 - 2007/1/1

N2 - Mounting evidence suggests that gliomas are comprised of differentiated tumor cells and brain tumor stem cells (BTSCs). BTSCs account for a fraction of total tumor cells, yet are apparently the sole cells capable of tumor initiation and tumor renewal. BTSCs have been identified as the CD133-positive fraction of human glioma, whereas their CD133-negative daughter cells have limited proliferative ability and are not tumorogenic. It is well established that the bulk tumor mass escapes immune surveillance by multiple mechanisms, yet little is known about the immunogenicity of the CD133-positive fraction of the tumor mass. We investigated the immunogenicity of CD133-positive cells in two human astrocytoma and two glioblastoma multiforme samples. Flow cytometry analyses revealed that the majority of CD133-positive cells do not express detectable MHC I or natural killer (NK) cell activating ligands, which may render them resistant to adaptive and innate immune surveillance. Incubating CD133-positive cells in interferon gamma (INF-gamma) significantly increased the percentage of CD133-positive cells that expressed MHC I and NK cell ligands. Furthermore, pretreatment of CD133-positive cells with INF-gamma rendered them sensitive to NK cell-mediated lysis in vitro. There were no consistent differences in immunogenicity between the CD133-positive and CD133-negative cells in these experiments. We conclude that CD133-posistive and CD133-negative glioma cells may be similarly resistant to immune surveillance, but that INF-gamma may partially restore their immunogenicity and potentiate their lysis by NK cells.

AB - Mounting evidence suggests that gliomas are comprised of differentiated tumor cells and brain tumor stem cells (BTSCs). BTSCs account for a fraction of total tumor cells, yet are apparently the sole cells capable of tumor initiation and tumor renewal. BTSCs have been identified as the CD133-positive fraction of human glioma, whereas their CD133-negative daughter cells have limited proliferative ability and are not tumorogenic. It is well established that the bulk tumor mass escapes immune surveillance by multiple mechanisms, yet little is known about the immunogenicity of the CD133-positive fraction of the tumor mass. We investigated the immunogenicity of CD133-positive cells in two human astrocytoma and two glioblastoma multiforme samples. Flow cytometry analyses revealed that the majority of CD133-positive cells do not express detectable MHC I or natural killer (NK) cell activating ligands, which may render them resistant to adaptive and innate immune surveillance. Incubating CD133-positive cells in interferon gamma (INF-gamma) significantly increased the percentage of CD133-positive cells that expressed MHC I and NK cell ligands. Furthermore, pretreatment of CD133-positive cells with INF-gamma rendered them sensitive to NK cell-mediated lysis in vitro. There were no consistent differences in immunogenicity between the CD133-positive and CD133-negative cells in these experiments. We conclude that CD133-posistive and CD133-negative glioma cells may be similarly resistant to immune surveillance, but that INF-gamma may partially restore their immunogenicity and potentiate their lysis by NK cells.

UR - http://www.scopus.com/inward/record.url?scp=34447648954&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34447648954&partnerID=8YFLogxK

U2 - 10.1007/s11060-006-9265-3

DO - 10.1007/s11060-006-9265-3

M3 - Article

C2 - 17077937

AN - SCOPUS:34447648954

VL - 83

SP - 121

EP - 131

JO - Journal of Neuro-Oncology

JF - Journal of Neuro-Oncology

SN - 0167-594X

IS - 2

ER -