Abstract
We previously characterized the expression of CD80 in different murine head and neck squamous cell carcinoma (HNSCC) clones derived following tumor progression in the absence of T cell-mediated immunity in severe combined immunodeficient (SCID) mice. We found that HNSCCs that did not express CD80 grew as progressors, while those that expressed CD80 were regressors when grown in immune-competent animals. In the present study, we characterized expression of a repertoire of immunoregulatory cytokines in these HNSCC lines, and found that HNSCCs that express cytokines IL-1α, IL-6, and GM-CSF do not express CD80, suggesting the hypothesis that these cytokines may down-modulate expression of CD80. Cytokine-conditioned medium from progressor HNSCC and recombinant IL-1α, IL-6, and GM-CSF caused a reduction of CD80 expression in regressor HNSCCs without affecting proliferation. Conversely, the decrease in CD80 expression in progressor HNSCCs could be restored by IFN-γ, a known inducer of CD80 expression. These data strongly suggest that high levels of cytokines IL-1α, IL-6, and GM-CSF expressed by tumor cells can down-regulate CD80 expression in HNSCC, and that IFN-γ can independently stimulate expression. These data provide evidence for a novel mechanism of cytokine-mediated down-modulation of CD80 during malignant progression of HNSCC that can be restored by IFN-γ.
| Original language | English |
|---|---|
| Pages (from-to) | 33-40 |
| Number of pages | 8 |
| Journal | Cancer Immunology, Immunotherapy |
| Volume | 53 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2004 |
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Keywords
- CD80
- Cytokines
- IFN-γ
- Regulation
- Squamous cell carcinoma
ASJC Scopus subject areas
- Cancer Research
- Immunology
- Oncology
Cite this
Cytokines IL-1α, IL-6, and GM-CSF constitutively secreted by oral squamous carcinoma induce down-regulation of CD80 costimulatory molecule expression : Restoration by interferon γ. / Thomas, Giovana; Chen, Zhong; Leukinova, Elena; Van Waes, Carter; Wen, Judy.
In: Cancer Immunology, Immunotherapy, Vol. 53, No. 1, 01.01.2004, p. 33-40.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cytokines IL-1α, IL-6, and GM-CSF constitutively secreted by oral squamous carcinoma induce down-regulation of CD80 costimulatory molecule expression
T2 - Restoration by interferon γ
AU - Thomas, Giovana
AU - Chen, Zhong
AU - Leukinova, Elena
AU - Van Waes, Carter
AU - Wen, Judy
PY - 2004/1/1
Y1 - 2004/1/1
N2 - We previously characterized the expression of CD80 in different murine head and neck squamous cell carcinoma (HNSCC) clones derived following tumor progression in the absence of T cell-mediated immunity in severe combined immunodeficient (SCID) mice. We found that HNSCCs that did not express CD80 grew as progressors, while those that expressed CD80 were regressors when grown in immune-competent animals. In the present study, we characterized expression of a repertoire of immunoregulatory cytokines in these HNSCC lines, and found that HNSCCs that express cytokines IL-1α, IL-6, and GM-CSF do not express CD80, suggesting the hypothesis that these cytokines may down-modulate expression of CD80. Cytokine-conditioned medium from progressor HNSCC and recombinant IL-1α, IL-6, and GM-CSF caused a reduction of CD80 expression in regressor HNSCCs without affecting proliferation. Conversely, the decrease in CD80 expression in progressor HNSCCs could be restored by IFN-γ, a known inducer of CD80 expression. These data strongly suggest that high levels of cytokines IL-1α, IL-6, and GM-CSF expressed by tumor cells can down-regulate CD80 expression in HNSCC, and that IFN-γ can independently stimulate expression. These data provide evidence for a novel mechanism of cytokine-mediated down-modulation of CD80 during malignant progression of HNSCC that can be restored by IFN-γ.
AB - We previously characterized the expression of CD80 in different murine head and neck squamous cell carcinoma (HNSCC) clones derived following tumor progression in the absence of T cell-mediated immunity in severe combined immunodeficient (SCID) mice. We found that HNSCCs that did not express CD80 grew as progressors, while those that expressed CD80 were regressors when grown in immune-competent animals. In the present study, we characterized expression of a repertoire of immunoregulatory cytokines in these HNSCC lines, and found that HNSCCs that express cytokines IL-1α, IL-6, and GM-CSF do not express CD80, suggesting the hypothesis that these cytokines may down-modulate expression of CD80. Cytokine-conditioned medium from progressor HNSCC and recombinant IL-1α, IL-6, and GM-CSF caused a reduction of CD80 expression in regressor HNSCCs without affecting proliferation. Conversely, the decrease in CD80 expression in progressor HNSCCs could be restored by IFN-γ, a known inducer of CD80 expression. These data strongly suggest that high levels of cytokines IL-1α, IL-6, and GM-CSF expressed by tumor cells can down-regulate CD80 expression in HNSCC, and that IFN-γ can independently stimulate expression. These data provide evidence for a novel mechanism of cytokine-mediated down-modulation of CD80 during malignant progression of HNSCC that can be restored by IFN-γ.
KW - CD80
KW - Cytokines
KW - IFN-γ
KW - Regulation
KW - Squamous cell carcinoma
UR - http://www.scopus.com/inward/record.url?scp=0742269447&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0742269447&partnerID=8YFLogxK
U2 - 10.1007/s00262-003-0433-4
DO - 10.1007/s00262-003-0433-4
M3 - Article
C2 - 14551747
AN - SCOPUS:0742269447
VL - 53
SP - 33
EP - 40
JO - Cancer Immunology and Immunotherapy
JF - Cancer Immunology and Immunotherapy
SN - 0340-7004
IS - 1
ER -