Celecoxib up-regulates the expression of the ζ chain of T cell receptor complex in tumor-infiltrating lymphocytes in human cervical cancer

Gabriella Ferrandina, Franco Oreste Ranelletti, Francesco Legge, Vanda Salutari, Enrica Martinelli, Andrea Fattorossi, Domenica Lorusso, Gianfranco Zannoni, Valerio Vellone, Amelia Paglia, Giovanni Scambia

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)2055-2060
Number of pages6
JournalClinical Cancer Research
Volume12
Issue number7 I
DOIs
Publication statusPublished - Apr 1 2006

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Celecoxib
Tumor-Infiltrating Lymphocytes
T-Cell Antigen Receptor
Uterine Cervical Neoplasms
Up-Regulation
Tryptases
Endostatins
Interleukin-12
Vascular Endothelial Growth Factor A
Neoplasms
Cytokines
Angiogenesis Inducing Agents
Lymphocyte Subsets
Biological Factors
Therapeutics
Interleukin-1
Interleukin-10
Interleukin-6
Research Design
Tumor Necrosis Factor-alpha

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ferrandina, G., Ranelletti, F. O., Legge, F., Salutari, V., Martinelli, E., Fattorossi, A., ... Scambia, G. (2006). Celecoxib up-regulates the expression of the ζ chain of T cell receptor complex in tumor-infiltrating lymphocytes in human cervical cancer. Clinical Cancer Research, 12(7 I), 2055-2060. https://doi.org/10.1158/1078-0432.CCR-05-2530

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 journalArticle

Ferrandina, G, Ranelletti, FO, Legge, F, Salutari, V, Martinelli, E, Fattorossi, A, Lorusso, D, Zannoni, G, Vellone, V, Paglia, A & Scambia, G 2006, 'Celecoxib up-regulates the expression of the ζ chain of T cell receptor complex in tumor-infiltrating lymphocytes in human cervical cancer', Clinical Cancer Research, vol. 12, no. 7 I, pp. 2055-2060. https://doi.org/10.1158/1078-0432.CCR-05-2530
Ferrandina, Gabriella ; Ranelletti, Franco Oreste ; Legge, Francesco ; Salutari, Vanda ; Martinelli, Enrica ; Fattorossi, Andrea ; Lorusso, Domenica ; Zannoni, Gianfranco ; Vellone, Valerio ; Paglia, Amelia ; Scambia, Giovanni. / Celecoxib up-regulates the expression of the ζ chain of T cell receptor complex in tumor-infiltrating lymphocytes in human cervical cancer. In: Clinical Cancer Research. 2006 ; Vol. 12, No. 7 I. pp. 2055-2060.
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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

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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.

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