In vitro exposure to paclitaxel modulates integrin expression by human T lymphocytes and inhibits T cell adhesion to breast carcinoma cells

Paclitaxel (Taxol) is a drug that is commonly used in the treatment of metastatic breast cancer. In this study, we investigated the effect of prior exposure to submaximal cytotoxic concentrations (EC₂₅ and EC ₅₀) of paclitaxel on the subsequent ability of human Jurkat T lymphocytes to adhere to monolayers of MDA-MB-435 human breast carcinoma cells. Jurkat T cells that survived culture for 24 h in the presence of paclitaxel (0.1 or 3 μg/ml) exhibited a diminished ability to adhere to MDA-MB-435 breast cancer cell monolayers. Flow cytometric analysis of paclitaxel-treated Jurkat T cells revealed reduced surface expression of α_L, α₄, α₅, and β₇ integrins, but normal β₁ integrin expression. These data suggest that paclitaxel interferes with the expression of α_Lβ ₂ (LFA-1), α₄β₁ (VLA-4), α₅β₁ (VLA-5), and α₄β ₇ (LPAM-1) adhesion molecules by surviving T cells. Blocking experiments with antibodies against α_L, β₄, α₅, β₁ and β₇ integrins revealed that adhesion of Jurkat T cells to MDA-MB-435 breast cancer cell monolayers was dependent upon α_L, α₄, and β₇ but not α₅or β₁ integrins. We conclude that prior exposure to paclitaxel caused a reduction in Jurkat T cell adhesion to MDA-MB-435 breast carcinoma cells by preventing optimal α_Lβ₂ and α₄β₇ interactions with their corresponding ligands on tumor cells. A similar effect by paclitaxel on T lymphocytes of breast cancer patients may compromise cell-mediated anti-tumor immune responses.