Chao T Y, Ting C S, Yeh M Y, Chang J Y, Wang C C, Chu T M
Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
Tumour Biol. 1995;16(4):230-42. doi: 10.1159/000217940.
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.
已知前列腺素E2（PGE2）可下调淋巴因子激活的杀伤（LAK）细胞活性。吲哚美辛是一种催化PGE2生物合成的环氧合酶抑制剂，已被证明可增强正常健康个体外周血单个核细胞产生的LAK细胞活性。本研究旨在探讨这种增强在癌症患者中是否也是一种常见现象。在15名正常健康个体和83名癌症患者中检测了有无吲哚美辛存在时产生的LAK细胞活性。配对数据分析显示，吲哚美辛显著增强了健康个体产生的LAK活性。吲哚美辛增强了无远处转移（TxNxM0）患者的LAK活性；但降低了有远处转移（TxNxM1）患者的LAK活性。在无远处转移的患者中，吲哚美辛对早期T分期（T1-2NxM0）患者的LAK活性有上调作用，而在晚期T分期（T3-4NxM0）患者中未检测到这种作用。吲哚美辛还显著增强了美国东部肿瘤协作组（ECOG）体能状态为1的癌症患者的LAK细胞生成，但显著抑制了体能状态为4的患者的LAK细胞生成。这些结果表明，吲哚美辛抑制了体能状态差或有远处转移性疾病的癌症患者的LAK细胞活性，而这些患者通常是过继性免疫治疗的对象。此外，在所有20名接受检查的癌症患者中，吲哚美辛均抑制了培养的LAK细胞培养基中PGE2的产生，这表明可能有其他尚未确定的因素或机制导致了吲哚美辛对LAK细胞活性的矛盾作用。
