Effects of indomethacin on lymphokine-activated killer cell activities in cancer patients

Tsu Yi Chao, Chin Shiong Ting, Ming Yang Yeh, Jang Yang Chang, Chang Chung Wang, T. Ming Chu

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Prostaglandin E2 (PGE2) is known to downregulate the generation of lymphokine-activated killer (LAK) cell activity. Indomethacin, an inhibitor of cyclooxygenase catalyzing the biosynthesis of PGE2, has been shown to augment LAK cell activities generated from peripheral blood mononuclear cells of normal healthy individuals. This study was undertaken to examine whether or not this augmentation is also a common phenomenon in cancer patients. LAK cell activities generated in the presence and the absence of indomethacin were examined in 15 normal healthy individuals and in 83 cancer patients. Paired data analysis revealed that indomethacin exhibited a significant augmentation of LAK activity generated from healthy individuals. Indomethacin enhanced LAK activity in patients with no distant metastases (TxNxM0); but depressed LAK activity in patients with distant metastases (TxNxM1). In patients without distant metastases, indomethacin showed an upregulating effect on LAK activity in those with an early T stage (T1-2NxM0), and no such effect was detected in those with a late T stage (T3-4NxM0). Indomethacin also significantly enhanced LAK cell generation in cancer patients with an ECOG performance status of 1, but significantly inhibited LAK cell generation in patients with a performance status of 4. These results indicated that indomethacin inhibited generation of LAK cell activity in cancer patients with a poor performance status or with distant metastatic disease, who normally would be the subjects of adoptive immunotherapy. Further, PGE2 production in cultured LAK cell medium was suppressed by indomethacin in all 20 cancer patients that were examined, suggesting that other yet to be identified factors or mechanisms may be responsible for the paradoxical effects of indomethacin on LAK cell activity.

Original languageEnglish
Pages (from-to)230-242
Number of pages13
JournalTumor Biology
Volume16
Issue number4
DOIs
Publication statusPublished - 1995
Externally publishedYes

Keywords

  • Indomethacin
  • Lymphokine-activated killer activity
  • Performance status
  • Stage of disease

ASJC Scopus subject areas

  • Cancer Research

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