@entity788 is a highly aggressive, treatment refractory disease and is the fourth leading cause of @entity204 in the United States. In @entity1 , 90% of @entity788 over-express altered forms of a @entity5 -associated antigen, @entity2355 (an epithelial mucin glycoprotein), which is a target for immunotherapy. Using a clinically relevant @entity19 model of @entity788 that demonstrates peripheral and central tolerance to @entity1 @entity2355 and develops spontaneous @entity5 of the pancreas, we have previously reported the presence of functionally active, low affinity, @entity2355 -specific precursor cytotoxic T cells (pCTLs). Hypothesis for this study is that @entity2355 -based immunization may enhance the low level @entity2355 -specific immunity that may lead to an effective anti- @entity5 response. Data demonstrate that @entity2355 peptide-based immunization elicits mature @entity2355 -specific CTLs in the peripheral lymphoid organs. The mature CTLs secrete @entity379 and are cytolytic against @entity2355 -expressing @entity5 cells in vitro. However, active CTLs that infiltrate the @entity5 microenvironment become cytolytically anergic and are tolerized to @entity2355 antigen, allowing the @entity5 to grow. We demonstrate that the CTL tolerance could be reversed at least in vitro with the use of anti-CD40 co-stimulation. The @entity5 cells secrete immunosuppressive cytokines, including @entity688 and @entity2533 that are partly responsible for the down-regulation of CTL activity. In addition, they down-regulate their MHC class I molecules to avoid immune recognition. @entity404 + @entity2902 + T regulatory cells, which secrete @entity688 , were also found in the @entity5 environment. Together these data indicate the use of several immune evasion mechanisms by @entity5 cells to evade CTL killing. Thus altering the @entity5 microenvironment to make it more conducive to CTL killing may be key in developing a successful anti- @entity5 immunotherapy.

XXXX -specific CTLs are non-functional within a @entity788 microenvironment.

@entity1 :: ('9606', 'Species') :: ['humans', 'human'] @entity788 :: ('MESH:D010190', 'Disease') :: ['pancreatic adenocarcinomas', 'Pancreatic cancer', 'pancreas cancer'] @entity404 :: ('920', 'Gene') :: ['CD4'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumors', 'cancer', 'pancreas tumor'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity688 :: ('3586', 'Gene') :: ['IL-10'] @entity2533 :: ('7040', 'Gene') :: ['TGF-beta'] @entity379 :: ('3458', 'Gene') :: ['IFN-gamma'] @entity2355 :: ('4582', 'Gene') :: ['MUC1'] @entity204 :: ('MESH:D003643', 'Disease') :: ['death'] @entity2902 :: ('3559', 'Gene') :: ['CD25']
@entity2355 :: (4582,Gene) :: ['MUC1']
