Cross regulation by IL-10 and IL-2/IL-12 of the helper T cells and the cytolytic activity of lymphocytes from malignant effusions of lung cancer patients

Yuh Min Chen, Wen Kuang Yang, Chou Chik Ting, Wen Ying Tsai, Den Mei Yang, Jacqueline Whang-Peng, Reury Perng Perng

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41 Citations (Scopus)

Abstract

Study objective: Our previous report demonstrated that there was impairment of local cellular immunity with elevated interleukin-10 (IL-10) and undetectable IL-12 in neoplastic pleural effusion. These findings suggest that the local immune reactions favor the T-helper type 2 (Th2) pathway instead of Th1 pathway. The present study was designed to examine whether local cellular immunity could be manipulated by IL-2 and/or IL-12 treatment, and to determine their effect on the helper T-cell pathways and the cytolytic activity of the effusion-associated lymphocytes (EALs). Design: Using malignant pleural effusions obtained from four patients suffering from adenocarcinoma of lung, we separated the tumor cells from the EALs with Ficol-Hypaque centrifugation, followed by Percoll density centrifugation. To test whether the cytolytic function of lymphocytes could be enhanced by culturing with IL-2 and/or IL-12, lymphocytes were incubated with recombinant IL-2 with/without IL-12 for 6 days. Following this, the tumoricidal activity was assessed in an overnight chromium-release assay. Autologous tumor cells for measuring specific antitumor activity, Daudi cells susceptible to lymphokine-activated killer cells, and NK-susceptible K562 cells were used as target cells. Measurements and results: After treatment in vitro with IL-2, IL-12, or IL-2 plus IL-12, the Th pathway shifted from Th2 to Th1 type (increased χ-interferon production). To further study the effect of cytokine treatment on the cytolytic activity of EALs, it was found that after 6-day, culturing, the EALs rafted to kill any of the three tumor targets, whereas the 6-day cultured peripheral blood lymphocytes (PBLs) gave low level of cytotoxicity against all three tumor targets. Stimulation with IL-2 alone partially restored the immunocompetence of EALs to kill the tumor targets. Stimulation with IL-12 alone showed no significant effect on their cytolytic activity. However, IL-12 synergized with IL-2 to increase the cytolytic activity of EALs and PBLs against autologous tumor targets. This synergistic effect was not found for Daudi cells and K562 cells. Conclusions: These results suggest that EALs activated with IL-12 in the presence of a low concentration of IL-2, which converted the EALs from Th2 pathway to Th1 pathway, could bean alternative source of antitumor effectors for adoptive immunotherapy of cancer.

Original languageEnglish
Pages (from-to)960-966
Number of pages7
JournalChest
Volume112
Issue number4
DOIs
Publication statusPublished - Jan 1 1997
Externally publishedYes

Keywords

  • Interleukin-2 (IL-2)
  • γ-Interferon (IFN-γ)

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

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