Abstract
Purpose: We evaluated the effects of celecoxib treatment on tumor-infiltrating lymphocyte (TIL) subsets [CD3+, CD4+,CD8+, CD25+, and T cell receptor (TCR)-ζ-expressing cells] and tryptase-positive mast cells in cervical tumors. Circulating levels of cytokines [interleukin (IL)-1β, IL-10, tumor necrosis factor-α, IL-6, and IL-12] and angiogenesis-modulating factors (vascular endothelial growth factor and endostatin) have also been analyzed. Experimental Design: Cervical tumor biopsies and blood samples were obtained at the time of diagnosis and after 10 days of celecoxib treatment (400 mg b.i.d., at 8:00 a.m. and 8:00 p.m.) in 27 cases. Immunohistochemistry and ELISA assays were used to assess the expression of biological factors in tumor tissue and circulating levels of cytokines and angiogenic molecules. Results: We showed a statistically significant increase in the percentage of TIL expressing the TCR-ζ chain after celecoxib treatment: indeed, in cases exposed to celecoxib, the percentage of TCR-ζ+ cells ranged from 5.0 to 50.0 (median, 22.5) with respect to baseline expression (range, 3.0-50.0; median, 10.0; P = 0.0016).There was no significant treatment-related difference in the percentage of CD3+, CD4+, CD8+, and CD25+ TIL as well as in tryptase-positive cells. IL-12 levels were significantly reduced in posttreatment samples with respect to baseline levels (P = 0.002). We also found a reduction in the circulating levels of vascular endothelial growth factor, and a statistically significant increase of serum endostatin levels (P = 0.035). Conclusions: We reported the first evidence in humans that celecoxib restores ζ expression by TIL in primary cervical tumors, suggesting that a positive modulation of immune function may serve as an additional mechanism supporting the antitumor effect of this class of drugs.
| Original language | English |
|---|---|
| Pages (from-to) | 2055-2060 |
| Number of pages | 6 |
| Journal | Clinical Cancer Research |
| Volume | 12 |
| Issue number | 7 I |
| DOIs | |
| Publication status | Published - Apr 1 2006 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
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Celecoxib up-regulates the expression of the ζ chain of T cell receptor complex in tumor-infiltrating lymphocytes in human cervical cancer. / Ferrandina, Gabriella; Ranelletti, Franco Oreste; Legge, Francesco; Salutari, Vanda; Martinelli, Enrica; Fattorossi, Andrea; Lorusso, Domenica; Zannoni, Gianfranco; Vellone, Valerio; Paglia, Amelia; Scambia, Giovanni.
In: Clinical Cancer Research, Vol. 12, No. 7 I, 01.04.2006, p. 2055-2060.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Celecoxib up-regulates the expression of the ζ chain of T cell receptor complex in tumor-infiltrating lymphocytes in human cervical cancer
AU - Ferrandina, Gabriella
AU - Ranelletti, Franco Oreste
AU - Legge, Francesco
AU - Salutari, Vanda
AU - Martinelli, Enrica
AU - Fattorossi, Andrea
AU - Lorusso, Domenica
AU - Zannoni, Gianfranco
AU - Vellone, Valerio
AU - Paglia, Amelia
AU - Scambia, Giovanni
PY - 2006/4/1
Y1 - 2006/4/1
N2 - Purpose: We evaluated the effects of celecoxib treatment on tumor-infiltrating lymphocyte (TIL) subsets [CD3+, CD4+,CD8+, CD25+, and T cell receptor (TCR)-ζ-expressing cells] and tryptase-positive mast cells in cervical tumors. Circulating levels of cytokines [interleukin (IL)-1β, IL-10, tumor necrosis factor-α, IL-6, and IL-12] and angiogenesis-modulating factors (vascular endothelial growth factor and endostatin) have also been analyzed. Experimental Design: Cervical tumor biopsies and blood samples were obtained at the time of diagnosis and after 10 days of celecoxib treatment (400 mg b.i.d., at 8:00 a.m. and 8:00 p.m.) in 27 cases. Immunohistochemistry and ELISA assays were used to assess the expression of biological factors in tumor tissue and circulating levels of cytokines and angiogenic molecules. Results: We showed a statistically significant increase in the percentage of TIL expressing the TCR-ζ chain after celecoxib treatment: indeed, in cases exposed to celecoxib, the percentage of TCR-ζ+ cells ranged from 5.0 to 50.0 (median, 22.5) with respect to baseline expression (range, 3.0-50.0; median, 10.0; P = 0.0016).There was no significant treatment-related difference in the percentage of CD3+, CD4+, CD8+, and CD25+ TIL as well as in tryptase-positive cells. IL-12 levels were significantly reduced in posttreatment samples with respect to baseline levels (P = 0.002). We also found a reduction in the circulating levels of vascular endothelial growth factor, and a statistically significant increase of serum endostatin levels (P = 0.035). Conclusions: We reported the first evidence in humans that celecoxib restores ζ expression by TIL in primary cervical tumors, suggesting that a positive modulation of immune function may serve as an additional mechanism supporting the antitumor effect of this class of drugs.
AB - Purpose: We evaluated the effects of celecoxib treatment on tumor-infiltrating lymphocyte (TIL) subsets [CD3+, CD4+,CD8+, CD25+, and T cell receptor (TCR)-ζ-expressing cells] and tryptase-positive mast cells in cervical tumors. Circulating levels of cytokines [interleukin (IL)-1β, IL-10, tumor necrosis factor-α, IL-6, and IL-12] and angiogenesis-modulating factors (vascular endothelial growth factor and endostatin) have also been analyzed. Experimental Design: Cervical tumor biopsies and blood samples were obtained at the time of diagnosis and after 10 days of celecoxib treatment (400 mg b.i.d., at 8:00 a.m. and 8:00 p.m.) in 27 cases. Immunohistochemistry and ELISA assays were used to assess the expression of biological factors in tumor tissue and circulating levels of cytokines and angiogenic molecules. Results: We showed a statistically significant increase in the percentage of TIL expressing the TCR-ζ chain after celecoxib treatment: indeed, in cases exposed to celecoxib, the percentage of TCR-ζ+ cells ranged from 5.0 to 50.0 (median, 22.5) with respect to baseline expression (range, 3.0-50.0; median, 10.0; P = 0.0016).There was no significant treatment-related difference in the percentage of CD3+, CD4+, CD8+, and CD25+ TIL as well as in tryptase-positive cells. IL-12 levels were significantly reduced in posttreatment samples with respect to baseline levels (P = 0.002). We also found a reduction in the circulating levels of vascular endothelial growth factor, and a statistically significant increase of serum endostatin levels (P = 0.035). Conclusions: We reported the first evidence in humans that celecoxib restores ζ expression by TIL in primary cervical tumors, suggesting that a positive modulation of immune function may serve as an additional mechanism supporting the antitumor effect of this class of drugs.
UR - http://www.scopus.com/inward/record.url?scp=33646267954&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646267954&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-05-2530
DO - 10.1158/1078-0432.CCR-05-2530
M3 - Article
C2 - 16609015
AN - SCOPUS:33646267954
VL - 12
SP - 2055
EP - 2060
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 7 I
ER -