PERIPHERAL-BLOOD T-LYMPHOCYTES AND LYMPHOCYTES INFILTRATING HUMAN CANCERS EXPRESS VASCULAR ENDOTHELIAL GROWTH-FACTOR - A POTENTIAL ROLE FORT-CELLS IN ANGIOGENESIS

CD3(+) peripheral blood T lymphocytes were evaluated for expression of vascular endothelial growth factor (VEGF), an endothelial cell mitoge n and potent angiogenic factor. VEGF mRNA expression was confirmed in CD3(+) cells and Jurkat cells, a human T-cell line, by reverse transcr iption-PCR and in CD4(+) and CD8(+) T cell subtypes by Northern blot h ybridization. Steady-state levels of VEGF mRNA were inducible in CD3() T cells by hypoxia, a knowm inducer of VEGF mRNA accumulation. Secre ted VEGF was detected in CD4(+) and CD8(+) T cell- and Jurkat cell-con ditioned medium, indicating that T lymphocytes are capable of exportin g bioactive concentrations of VEGF into the extracellular space. Human prostate and bladder cancers (prostatic adenocarcinoma and transition al cell carcinomas) were evaluated for VEGF mRNA expression by in situ hybridization. Tumor-infiltrating lymphocytes (TIL), identifiable imm unocytochemically as T cells, along with tumor cells in these cancers, expressed VEGF mRNA. Tn in bladder cancers could be labeled with a sp ecific anti-VEGF mAb, indicating that TIL are likely to be able to sec rete VEGF protein in situ at bioactive concentrations. The finding tha t peripheral T cells and TIL in human tumors synthesize a factor known to be a specific mediator of neovascularization suggests a role for T lymphocytes as cellular effecters of angiogenesis.