Effects of Pulsing Procedure of Interleukin-12 in Combination with Interleukin-2 on the Activation of Peripheral Blood Lymphocytes Derived from Patients with Hepatocellular Carcinoma

Tomoyuki Sawayama, Kohsaku Sakaguchi, Tomonori Senoh, Takeyuki Ohta, Mamoru Nishimura, Akinobu Takaki, Takao Tsuji, Yasushi Shiratori

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6 Citations (Scopus)


In patients with hepatocellular carcinoma (HCC), natural killer (NK) cell activity decreases significantly, and the reduced activity may be associated with the progression of HCC. In this study we evaluated the effects of pulsing with interleukin (IL)-2 and/or IL-12 on the activation of freshly isolated peripheral blood lymphocytes (PBL) derived from patients with HCC. PBL obtained from 9 HCC patients, 4 liver cirrhosis patients, and 9 normal subjects were cultured in the presence of IL-2 and/or IL-12. After 24 h of incubation, the levels of interferon (IFN)-γ and tumor necrosis factor (TNF)-α presented in the supernatants were determined by enzyme-linked immunosorbent assay (ELISA). The IFN-γ and TNF-α production of PBL pulsed by a combination of IL-2 and IL-12 was significantly higher than those of PBL stimulated by either IL-2 or IL-12 alone. The mRNA encoding perform, granzyme B, as well as IFN-γ and TNF-α, were markedly enhanced in PBL stimulated with a combination of IL-12 and IL-2. The pulsing procedure of IL-12 in combination with IL-2 resulted in the increase of IFN-γ and TNF-α, and the expression of perform and granzyme B mRNA in PBL obtained from HCC patients, as well as in those obtained from normal subjects. These results indicate that adoptive immunotherapy based on PBL pulsed with a combination of IL-2 and IL-12 may be a promising adjunctive strategy for HCC treatment.

Original languageEnglish
Pages (from-to)285-292
Number of pages8
JournalActa medica Okayama
Issue number6
Publication statusPublished - Dec 1 2003



  • Granzyme B
  • Hepatocellular carcinoma (HCC)
  • Interferon (IFN)-γ
  • Interleukin (IL)-12
  • Interleukin (IL)-2

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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