Indomethacin Treatment of Mice with Premalignant Oral Lesions Sustains Cytokine Production and Slows Progression to Cancer
| Autor: | Sara D. Johnson, M. Rita I. Young |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
0301 basic medicine Pathology medicine.medical_specialty medicine.medical_treatment T cell Immunology Spleen HNSCC Lesion 03 medical and health sciences 0302 clinical medicine Immune system medicine Immunology and Allergy Lymph node Original Research business.industry medicine.disease Head and neck squamous-cell carcinoma cytokines 3. Good health stomatognathic diseases 030104 developmental biology medicine.anatomical_structure Cytokine 030220 oncology & carcinogenesis premalignant oral lesions head and neck cancer Lymph immune medicine.symptom lcsh:RC581-607 business |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 7 (2016) |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2016.00379 |
| Popis: | Current treatment options for head and neck squamous cell carcinoma (HNSCC) patients are often ineffective due to tumor localized and systemic immunosuppression. Using the 4-NQO mouse model of oral carcinogenesis, this study showed that premalignant oral lesion cells produce higher levels of the immune modulator, PGE2, compared to HNSCC cells. Inhibiting prostaglandin production of premalignant lesion cells with the pan-cyclooxygenase inhibitor indomethacin stimulated their induction of spleen cell cytokine production. In contrast, inhibiting HNSCC prostaglandin production did not stimulate their induction of spleen cell cytokine production. Treatment of mice bearing premalignant oral lesions with indomethacin slowed progression of premalignant oral lesions to HNSCC. Flow cytometric analysis of T cells in the regional lymph nodes of lesion-bearing mice receiving indomethacin treatment showed an increase in lymph node cellularity and in the absolute number of CD8+ T cells expressing IFN-γ compared to levels in lesion-bearing mice receiving diluent control treatment. The cytokine-stimulatory effect of indomethacin treatment was not localized to regional lymph nodes but was also seen in the spleen of mice with premalignant oral lesions. Together, these data suggest that inhibiting prostaglandin production at the premalignant lesion stage boosts immune capability and improves clinical outcomes. |
| Databáze: | OpenAIRE |
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