Immunoregulation in cancer-bearing hosts. Down-regulation of gene expression and cytotoxic function in CD8+ T cells.

摘要: The causes of the decreased immune responsiveness in tumor-bearing hosts are incompletely understood. impact a response cancer patients on clinical immunotherapy trials has not been evaluated. present report demonstrates marked decrease therapeutic efficacy adoptively transferred T lymphocytes obtained from murine bearing tumor for greater than 30 days [late mice (TBM)] as compared with normal and less 21 (early TBM). In vitro analysis functions late TBM showed an apparently proliferative to anti-CD3 IL-2 adequate lymphokine production CD4+ cells, but significant cytotoxic function CD8+ cells. cytotoxicity was because cell-mediated suppression. expression granzyme B mRNA significantly delayed magnitude cells TBM. Culture supernatants two unrelated cell lines were able inhibit activity vitro. tumor-derived suppressive factor is transforming growth factor-beta (TGF-beta), it further characterized. data suggest that one potential mechanism responsible immunologic defects large burdens tumor-induced defect compromises effector