Immunomodulatory effects of interleukin-12 on human tumor-infiltrating lymphocytes

J. Valerie, Ravan Andrews, Deric D. Schoof, Monica M. Bertagnolli, George E. Peoples, Simon Goedegebuure, Timothy Eberlein

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41 Scopus citations

Abstract

Interleukin (IL)-12 is a recently described cytokine with multiple immunoregulatory effects on various lymphoid populations, including peripheral blood lymphocytes (PBL), natural killer (NK) cells, and T-cell subsets. We examined the effects of recombinant IL-12 on the immune function of human tumor infiltrating lymphocytes (TIL) from several different tumor types. At an optimal concentration of 50 IU/ml, IL-12 acted as a co-stimulant for TIL recently activated with anti-CD3 antibodies, giving stimulation indices between 2.6 and 9.9. This co-stimulatory effect was independent of IL-2 and was not inhibited by neutralizing antibody to human IL-2. When IL-2 and IL-12 were used synchronously as co-mitogenic stimuli in culture with activated TIL, the effect on proliferation was additive. This additive effect held true over a range of suboptimal concentrations of IL-2 and in different TIL populations. IL-12 did not enhance non-major histocompatability complex (MHC)-restricted cytotoxicity in the TIL populations tested. TIL cultured with IL-12 killed more autologous tumor targets than TIL maintained in media alone at identical effector/target (E/T) ratios. This effect on cytotoxicity was not as great as that seen in TIL maintained in low-dose IL-2. Co-culture with IL-12 did not change the phenotype of TIL used in these assays. The importance of these findings and possible uses in immunotherapy are discussed.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalJournal of Immunotherapy
Volume14
Issue number1
DOIs
StatePublished - Jul 1993

Keywords

  • Cytokines
  • Immunotherapy
  • Interleukin-12
  • Tumor infiltrating lymphocytes

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