Matsunaga H, Kuwahara Y, Kusugami K, Morise K, Shimokata K
First Department of Internal Medicine, Nagoya University of School of Medicine, Japan.
Gastroenterol Jpn. 1988 Oct;23(5):527-33. doi: 10.1007/BF02779484.
Natural killer (NK) activity, lymphokine-activated killer (LAK) activity and interferon-gamma (IFN-gamma) producing activity of peripheral blood mononuclear cells (PBMC) and regional lymph node mononuclear cells (LNMC) were studied in 23 previously untreated cases of colorectal cancer. NK and LAK activities were significantly lower in LNMC than in PBMC. Patients showed depressed NK and LAK activities in PBMC. In the Dukes C group, especially, both NK activity and LAK activity decreased compared to control patients. NK and LAK activities of PBMC decreased as the grade of invasion to lymphatic channels progressed. LAK activity positively correlated with NK activity in PBMC. Patients with high LAK activity showed high IFN-gamma production in both controls and Dukes A . B patients. However, in Dukes C patients, no relationship between LAK activity and IFN-gamma production was observed. We conclude that the depressed NK and LAK activities of PBMC reflect the local lymphatic invasion and that IFN-gamma involvement in LAK cell generation is impaired in advanced cancer patients. More fundamental studies should be carried out before clinical trials of adoptive immunotherapy using LAK cells, because LAK activity is not induced sufficiently in advanced cancer.
在23例未经治疗的结直肠癌患者中，研究了外周血单个核细胞（PBMC）和区域淋巴结单个核细胞（LNMC）的自然杀伤（NK）活性、淋巴因子激活的杀伤（LAK）活性以及干扰素-γ（IFN-γ）产生活性。LNMC中的NK和LAK活性显著低于PBMC。患者的PBMC中NK和LAK活性降低。尤其是在Dukes C组中，与对照患者相比，NK活性和LAK活性均降低。随着淋巴管浸润程度的进展，PBMC的NK和LAK活性降低。PBMC中的LAK活性与NK活性呈正相关。LAK活性高的患者在对照组以及Dukes A、B期患者中均表现出高IFN-γ产生。然而，在Dukes C期患者中，未观察到LAK活性与IFN-γ产生之间的关系。我们得出结论，PBMC中NK和LAK活性降低反映了局部淋巴浸润，并且在晚期癌症患者中，IFN-γ参与LAK细胞生成的过程受损。在使用LAK细胞进行过继性免疫治疗的临床试验之前，应该进行更基础的研究，因为在晚期癌症中LAK活性诱导不足。
