Chemoattractants MDC and TARC are secreted by malignant B-cell precursors following CD40 ligation and support the migration of leukemia-specific T cells

The use of tumor cells as vaccines in cancer immunotherapy is critically de pendent on their capacity to initiate and amplify tumor-specific immunity. Optimal responses may require the modification of the tumor cells not only to increase their Immunogenicity but also to improve their ability to recru it effector cells to the tumor sites or sites of tumor antigen exposure. It has been reported that CD40 crosslinking of acute lymphoblastic leukemia ( ALL) cells significantly increases their immunogenicity and allows the gene ration and expansion of autologous antileukemia cytotoxic T lymphocytes. Th is study demonstrates that the CD40 ligation of these tumor cells also indu ces the secretion of the CC-chemokines MDC and TARC. Supernatants from mali gnant cells cultured In the presence of sCD40L promote the migration of act ivated T cells that express CCR4, the common specific receptor for MDC and TARC. More importantly, the supernatants from CD40-immunogenicity and allow s the generation and expansion of autologous antileukemia cytotoxic T lymph ocytes. This study demonstrates that the CD40 ligation of these tumor cells also induces the secretion of the CC-chemokines MDC and TARC. Supernatants from malignant cells cultured In the presence of sCD40L promote the migrat ion of activated T cells that express CCR4, the common specific receptor fo r MDC and TARC. More importantly, the supernatants from CD40-stimulated tum or cells also support the transendothelial migration of autologous CCR4(+) antileukemia T cells. Therefore, the results demonstrate that the delivery to leukemia cells of a single physiologic signal, that is, CD40 cross-linki ng, simultaneously improves tumor cell immunogenicity and induces potent ch emoattraction for T cells.