Synergism between immunostimulation and prevention of surgery-induced immune suppression: An approach to reduce post-operative tumor progression
| Autor: | Inbal Ben-Ami Bartal, Ella Rosenne, Roi Avraham, Shelly Inbar, Marganit Benish, Shamgar Ben-Eliyahu |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
Lung Neoplasms Prostaglandin Antagonists Survival medicine.medical_treatment Adrenergic beta-Antagonists Indomethacin Immunology Article Immune tolerance Behavioral Neuroscience Catecholamines Hormone Antagonists Postoperative Complications Immune system Adjuvants Immunologic Immunity Cell Line Tumor Immune Tolerance medicine Animals Cyclooxygenase Inhibitors Laparotomy Endocrine and Autonomic Systems business.industry Immunosuppression Neoplasms Experimental Immunotherapy Flow Cytometry medicine.disease Interleukin-12 Primary tumor Rats Inbred F344 Rats Surgery Killer Cells Natural Nadolol Poly I-C Tumor progression Disease Progression Interleukin 12 business |
| Zdroj: | Brain, Behavior, and Immunity. 24:952-958 |
| ISSN: | 0889-1591 |
| DOI: | 10.1016/j.bbi.2010.03.010 |
| Popis: | Background: A unique opportunity to eradicate cancer is presented immediately after the excision of the primary tumor, but surgical procedures often induce the release of immunosuppressing factors that render cell mediated immunity ineffective. Here we tested the hypothesis that integration of peri-operative immunostimulation and blockade of immunosuppression could synergistically improve post-operative anti-metastatic immunity and long-term survival. Methods: Two syngeneic tumor models in F344 rats were employed, studying post-operative tumor progression. In the first model, survival following laparotomy and CRNK-16 leukemia was studied. Rats were peri-operatively treated with the immuno-stimulant poly I-C (5 × 0.2 mg/kg/inj), with catecholamine- and prostaglandin-blockers (shown to prevent post-operative immunosuppression: 4.5 mg/kg nadolol, 4 mg/kg indomethacin), with both interventions, or with neither. Long-term survival was assessed thereafter. The second model used the MADB106 mammary adenocarcinoma, assessing its lung tumor retention (LTR) following i.v. inoculation, as well as host marginating-pulmonary NK numbers and activity against this tumor. IL-12 was employed for immunostimulation (4 × 1.5 μg/kg/inj), with and without the above blockers. Results: Post-operative CRNK-16 survival rates were significantly improved only by the integrated approach of immune stimulation and endocrine blockers. Post-operative MADB106 LTR was additively reduced by the two interventions. Importantly, while IL-12 increased pulmonary NK cytotoxicity against MADB106, surgery markedly suppressed this cytotoxicity in both IL-12 and vehicle treated animals. The blockers prevented this suppression per lung and per single NK cell. Conclusions: Immunostimulation could be rendered ineffective post-operatively due to immunosuppression; therefore integrating endocrine-blocker therapies into the realm of peri-operative immunotherapy could optimize immune control over residual disease, potentially improving clinical outcomes. |
| Databáze: | OpenAIRE |
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