Reversal of multiple-site tumor cell-induced immunosuppression by specific cytokines and pharmacological agents
| Autor: | Jie Wang, Myrthel E. Hargrove, Chou-Chik Ting |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
medicine.medical_treatment
T cell Biology Lymphocyte Activation Exocytosis Granzymes Immune tolerance Amiloride Mice Immune system Adjuvants Immunologic Cyclosporin a medicine Immune Tolerance Tumor Cells Cultured Animals Pharmacology Cytolytic granule Lymphokines Serine Endopeptidases Lymphokine Neoplasms Experimental Glutathione Killer Cells Natural Mice Inbred C57BL Cytokine medicine.anatomical_structure Immunology Myeloid-derived Suppressor Cell Cancer research Cytokines Female Interleukin-4 Immunocompetence Immunosuppressive Agents |
| Zdroj: | Immunopharmacology. 30(2) |
| ISSN: | 0162-3109 |
| Popis: | The present study explores a model for tumor cell-induced immunosuppression and reversal of suppression by cytokines and other pharmacological agents. To simulate tumor-cell-induced suppression, a panel of suppressor agents which included CsA (cyclosporin A), SSP (staurosporine), BSO (L-buthionine-[S,R]-sulfoximine) and PMA, and a panel of anti-suppressor agents which included IL-2, IL-4, GSH (glutathione) and amiloride, were tested. These suppressor/anti-suppressor agents acted differently on four specific sites of the immune arm that affected the alpha CD3-induced T cell proliferative and cytotoxic responses. They included (1) IL-2 production, (2) PKC-regulated cytolytic granule production, (3) GSH-regulated maturation of functional granules, and (4) granule exocytosis. When a single suppressor agent was used, all the suppressor agents tested in this study inhibited the generation of alpha CD3-induced activated killer cells (CD3-AK), whereas alpha CD3-induced proliferation was inhibited by CsA, BSO, and EL-4 tumor cells. Except for EL-4, suppression induced by a single suppressor agent could be corrected by an appropriate single anti-suppressor agent. Multiple suppressor agents induced profound suppression of CD3-AK response. In most cases, multiple anti-suppressor agents were required to correct the immune defects induced by multiple suppressor agents. Finally, EL-4 tumor-cell-induced immunosuppression could not be corrected by any single anti-suppressor agent tested, but a combination of IL-4, GSH and amiloride fully restored the CD3-AK response. These results suggest that tumor cells may induce multiple immune defects that require multiple anti-suppressor agents for correcting the defects to restore the host immunocompetence. |
| Databáze: | OpenAIRE |
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