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*
Department of Biochemistry, University of Illinois at Chicago, Chicago, IL 60680; and
The Ben May Institute for Cancer Research, the Committee on Immunology, and the Department of Pathology, University of Chicago, Chicago, IL 60637
We have previously shown that low dose melphalan
(L-phenylalanine mustard; L-PAM) therapy
of hitherto immunosuppressed mice bearing a large (20-mm) s.c. MOPC-315
tumor leads to the acquisition of potent CD8+ T
cell-mediated antitumor immunity which in turn eradicates the large
tumor burden not eradicated by the direct antitumor effects of the
drug. Here we show the preferential importance of the B7-2
costimulatory molecule for the curative effectiveness of low dose
L-PAM for mice bearing a large MOPC-315 tumor by
demonstrating that treatment with anti-B7-2 mAb, but not
anti-B7-1 mAb, reduced the percentage of mice cured by the low dose
L-PAM. In addition, we show the preferential importance of
the B7-2 molecule for the low dose L-PAM-induced
acquisition of the ability of tumor-infiltrating lymphocytes from
MOPC-315 tumor bearers to secrete IL-2 and IFN-
as well as to exert
an anti-MOPC-315 CTL effect. The preferential importance of the
B7-2 molecule may be due to the higher level of B7-2 than of B7-1
expression on B220+ cells and on tumor cells from the s.c.
tumor nodule of low dose L-PAM-treated MOPC-315 tumor
bearers and the selective up-regulation of the B7-2 molecule in the
draining of these mice. Thus, the B7-2 molecule plays a dominant role
in the acquisition of T cell-dependent tumor-eradicating immunity in
low dose L-PAM-treated mice bearing a large MOPC-315 tumor,
suggesting that one of the mechanisms by which chemotherapy may enhance
antitumor immunity is through up-regulation of critical costimulatory
molecules that enhance antitumor responses.
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