PURPOSE: In @entity11 -in contrast to various other cancers-the impact of T-lymphocytes on clinical outcome is not clear. We investigated the clinical relevance and regulation of T-cell infiltration in @entity11 . EXPERIMENTAL DESIGN: T-cell subpopulations from entire sections of 93 WHO  II-IV @entity11 were computationally identified using markers CD3, @entity405 , and @entity403 ; survival analysis was then done on primary @entity463 (pGBM). Endothelial cells expressing cellular adhesion molecules (CAM) were similarly computationally quantified from the same @entity11 tissues. Influence of prominent cytokines (as measured by ELISA from 53 WHO  II-IV @entity11 lysates) on CAM-expression in @entity11 -isolated endothelial cells was determined using flow cytometry. The functional relevance of the cytokine-mediated CAM regulation was tested in a transmigration assay using @entity11 -derived endothelial cells and autologous T-cells. RESULTS: Infiltration of all T-cell subsets increased in high-grade @entity5 . Most strikingly, within pGBM, elevated numbers of intratumoral effector T cells (T(eff), cytotoxic and helper) significantly correlated with a better survival; regulatory T cells were infrequently present and not associated with @entity11 @entity1 outcome. Interestingly, increased infiltration of T(eff) cells was related to the expression of @entity2071 on the vessel surface. Transmigration of autologous T cells in vitro was markedly reduced in the presence of CAM-blocking antibodies. We found that @entity2533 molecules impeded transmigration and downregulated CAM-expression on @entity11 -isolated endothelial cells; blocking @entity2533 receptor signaling increased transmigration. CONCLUSIONS: This study provides comprehensive and novel insights into occurrence and regulation of T-cell infiltration in @entity11 . Specifically, targeting @entity2533 and @entity6474 might improve intratumoral T-cell infiltration and thus enhance effectiveness of immunotherapeutic approaches.

Effector T-cell infiltration positively impacts survival of @entity463 @entity1 and is impaired by tumor-derived XXXX .

@entity1 :: ('9606', 'Species') :: ['patient'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumors'] @entity11 :: ('MESH:D005910', 'Disease') :: ['GBM', 'glioma', 'gliomas'] @entity2533 :: ('7040', 'Gene') :: ['TGF-b', 'TGF-b1'] @entity403 :: ('50943', 'Gene') :: ['Foxp3'] @entity463 :: ('MESH:D005909', 'Disease') :: ['glioblastomas'] @entity6474 :: ('7042', 'Gene') :: ['TGF-b2'] @entity2071 :: ('3383', 'Gene') :: ['ICAM-1'] @entity405 :: ('925', 'Gene') :: ['CD8']
@entity2533 :: (7040,Gene) :: ['TGF-b']
