Interleukin-12 augments cytolytic activity of peripheral blood lymphocytes from patients with hematologic and solid malignancies

Robert J. Soiffer, Michael Robertson, Christine Murray, Keith Cochran, Jerome Ritz

Research output: Contribution to journalArticle

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Abstract

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 hematologie 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.

Original languageEnglish (US)
Pages (from-to)2790-2796
Number of pages7
JournalBlood
Volume82
Issue number9
StatePublished - Nov 1 1993
Externally publishedYes

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Lymphocytes
Hematologic Neoplasms
Interleukin-12
Blood
Blood Cells
Interleukin-2
Neoplasms
Tumors
Homologous Transplantation
Cytotoxicity
Bone Marrow Transplantation
Bone
Transplants
Defects
Immunologic Factors
Natural Killer Cells
Healthy Volunteers
Cells
Cytokines

ASJC Scopus subject areas

  • Hematology

Cite this

Interleukin-12 augments cytolytic activity of peripheral blood lymphocytes from patients with hematologic and solid malignancies. / Soiffer, Robert J.; Robertson, Michael; Murray, Christine; Cochran, Keith; Ritz, Jerome.

In: Blood, Vol. 82, No. 9, 01.11.1993, p. 2790-2796.

Research output: Contribution to journalArticle

Soiffer, Robert J. ; Robertson, Michael ; Murray, Christine ; Cochran, Keith ; Ritz, Jerome. / Interleukin-12 augments cytolytic activity of peripheral blood lymphocytes from patients with hematologic and solid malignancies. In: Blood. 1993 ; Vol. 82, No. 9. pp. 2790-2796.
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