Immunoregulation in cancer-bearing hosts. Down-regulation of gene expression and cytotoxic function in CD8+ T cells
| Autor: | C M, Loeffler, M J, Smyth, D L, Longo, W C, Kopp, L K, Harvey, H R, Tribble, J E, Tase, W J, Urba, A S, Leonard, H A, Young |
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| Rok vydání: | 1992 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cytotoxicity Immunologic Time Factors Lymphoma Tumor Necrosis Factor-alpha CD8 Antigens Carcinoma Lymphocyte Cooperation Serine Endopeptidases Immunization Passive Gene Expression Neoplasms Experimental T-Lymphocytes Helper-Inducer In Vitro Techniques Granzymes Mice Inbred C57BL Mice T-Lymphocyte Subsets Colonic Neoplasms Animals RNA Messenger Carcinoma Renal Cell T-Lymphocytes Cytotoxic |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 149(3) |
| ISSN: | 0022-1767 |
| Popis: | The causes of the decreased immune responsiveness in tumor-bearing hosts are incompletely understood. The impact of a decreased immune response in cancer patients on the clinical response in immunotherapy trials has not been evaluated. The present report demonstrates a marked decrease in the therapeutic efficacy of adoptively transferred T lymphocytes obtained from murine hosts bearing tumor for greater than 30 days [late tumor-bearing mice (TBM)] as compared with normal mice and mice bearing tumor for less than 21 days (early TBM). In vitro analysis of the functions of the T lymphocytes from late TBM showed an apparently normal proliferative response to anti-CD3 and IL-2 with adequate lymphokine production from CD4+ cells, but a significant decrease in the cytotoxic function of CD8+ cells. The decreased cytotoxicity was not because of cell-mediated suppression. The expression of granzyme B mRNA was significantly delayed and decreased in magnitude in CD8+ cells from late TBM. Culture supernatants from two unrelated tumor cell lines were able to inhibit the cytotoxic activity of normal CD8+ cells in vitro. The tumor-derived suppressive factor is not transforming growth factor-beta (TGF-beta), but it has not been further characterized. The data suggest that one potential mechanism responsible for immunologic defects in patients with large tumor burdens is a tumor-induced defect that compromises the function of CD8+ effector T cells. |
| Databáze: | OpenAIRE |
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