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Blood, 1 August 2001, Vol. 98, No. 3, pp. 533-540
CHEMOKINES
Chemoattractants MDC and TARC are secreted by malignant B-cell
precursors following CD40 ligation and support the migration of
leukemia-specific T cells
Paolo Ghia,
Pietro Transidico,
J. Pedro Veiga,
Christoph Schaniel,
Federica Sallusto,
Kouji Matsushima,
Stephen E. Sallan,
Antonius G. Rolink,
Alberto Mantovani,
Lee M. Nadler, and
Angelo A. Cardoso
From the Department of Adult Oncology and Pediatric
Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston,
MA; Istituto per la Ricerca e la Cura del Cancro, Ospedale Mauriziano
"Umberto I," and University of Torino, Candiolo, Italy; Istituto di
Ricerche Farmacologiche Mario Negri, Milano, Italy; Basel Institute for
Immunology, Basel, Switzerland; and Tokyo Medical School, Tokyo, Japan.
The use of tumor cells as vaccines in cancer immunotherapy is
critically dependent 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 recruit effector cells to the tumor sites
or sites of tumor antigen exposure. It has been reported that CD40
cross-linking of acute lymphoblastic leukemia (ALL) cells significantly
increases their immunogenicity and allows the generation and expansion
of autologous antileukemia cytotoxic T lymphocytes. 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
migration of activated T cells that express CCR4, the common
specific receptor for MDC and TARC. More importantly, the
supernatants from CD40-stimulated tumor 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-linking, simultaneously improves tumor cell immunogenicity and
induces potent chemoattraction for T cells.
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