Potential Role for T Cells in Angiogenesis A Human Cancers Express Vascular Endothelial Growth Factor: Peripheral Blood T Lymphocytes and Lymphocytes Infiltrating

CD3* peripheral blood T lymphocytes were evaluated for expression of vascular endothelial growth factor (VEGF), an endothelial cell mitogen and potent angiogenic factor. VEGF mRNA expression was confirmed in CD3+ cells and Jurkat cells, a human T-cell line, by reverse transcriptionPCR and in ( ÕU and CDS' T cell subtypes by Northern blot hybridiza tion. Steady-state levels of VEGF mRNA were inducible in CD3* T cells by hypoxia, a known inducer of VEGF mRNA accumulation. Secreted VEGF was detected in (1)4 and ( I)S T celland Jurkat cell-conditioned medium, indicating that T lymphocytes are capable of exporting bioactive concentrations of VEGF into the extracellular space. Human prostate and bladder cancers (prostatic adenocarcinoma and transitional cell carcino mas) were evaluated for VEGF mRNA expression by in situ hybridization. Tumor-infiltrating lymphocytes (TIL), identifiable immunocytochemically as T cells, along with tumor cells in these cancers, expressed VEGF mRNA. TIL in bladder cancers could be labeled with a specific anti-VEGF in \l>. indicating that TIL are likely to be able to secrete VEGF protein in situ at bioactive concentrations. The finding that 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 effec tors of angiogenesis.