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Interleukin-12 augments cytolytic activity of peripheral blood lymphocytes
from patients with hematologic and solid malignancies
RJ Soiffer, MJ Robertson, C Murray, K Cochran and J Ritz
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA
02115.
Interleukin-12 (IL-12) is a heterodimeric 70-kD cytokine that can enhance
the activity of cytotoxic effector cells. Although IL-12 shares some
functional properties with interleukin-2 (IL-2), it appears to act via a
distinct mechanism. In this report, we examined the effects of IL- 12 on
the cytolytic activity and proliferation of peripheral blood mononuclear
cells (PBMC) obtained from patients with malignant disease. PBMC from two
groups of patients were evaluated. The first group consisted of 12
individuals with metastatic solid tumors. PBMC from these patients
demonstrated a marked defect in their ability to lyse natural killer
(NK)-sensitive targets (K562) compared with normal volunteers. Overnight
incubation with IL-12 (35 pmol/L) corrected this defect. The effect of 35
pmol/L of IL-12 on cytotoxicity was similar to that of 3 nmol/L of IL-2. In
contrast, this concentration of IL-12 had little effect on cytolytic
activity against an NK-resistant cell line (COLO 205). When IL-12 was added
to PBMC obtained from cancer patients who were being treated with low-dose
IL-2 in vivo, a dramatic increase in cytolytic activity against both
NK-sensitive and -resistant tumor targets was observed. Unlike IL-2, IL-12
failed to stimulate proliferation of resting PBMC from cancer patients
significantly. The second group of patients we studied comprised 13
patients who had recently undergone allogeneic bone marrow transplantation
(BMT) for hematologic malignancy. In resting PBMC from these transplant
recipients, IL-12 was capable of enhancing cytotoxicity against both NK-
sensitive and -resistant tumor targets. Our findings indicate that IL- 12
can restore defective NK activity of PBMC from patients with metastatic
cancer, as well as enhance cytolytic function of PBMC from patients after
allogeneic BMT. The clinical use of IL-12 as an immunomodulator in patients
with malignancy merits further consideration.
Volume 82,
Issue 9,
pp. 2790-2796,
11/01/1993
Copyright © 1993 by The American Society of Hematology
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