Bailet J W, Lichtenstein A, Chen G, Mickel R A
Division of Head and Neck Surgery, Veterans Affairs Medical Center West Los Angeles, USA.
Arch Otolaryngol Head Neck Surg. 1997 Aug;123(8):855-62. doi: 10.1001/archotol.1997.01900080089011.
Immunosuppression in patients with head and neck cancer is well recognized. Previous investigations have demonstrated graded immunosuppression that becomes more pronounced as lymphocyte activity is measured closer to the primary neoplasm. In fresh tumors, a soluble factor has been identified that may partly account for the observed graded immunosuppression.
To examine the effect of soluble factors produced by head and neck sqamous cell carcinoma cell lines on the generation of lymphokine activated killer cell cytotoxicity and peripheral blood lymphocyte proliferation induced by interleukin 2, concanavalin A, and phytohemagglutinin.
Conditioned supernatant fluids were generated in a 4-day incubation period, using 5 head and neck squamous cell carcinoma cell lines, and were assayed for the ability to inhibit the generation of lymphokine activated killer cell cytotoxicity and naive peripheral blood lymphocyte proliferation induced by interleukin 2, concanavalin A, and phytohemagglutinin.
All conditioned supernatant fluids significantly inhibited the generation of lymphokine activated killer cell cytotoxicity relative to controls, and this inhibition was dose dependent. In contrast, supernatant fluids from a myelogenous leukemic tumor cell line, K562, and an ovarian epithelial cell line, SKOV-3, failed to inhibit cytotoxicity. Supernatant fluids conditioned with head and neck squamous cell carcinoma cell lines also profoundly inhibited the naive peripheral blood lymphocyte proliferation induced by interleukin 2, concanavalin A, and phytohemagglutinin.
These studies demonstrate that the cell lines of head and neck squamous cell carcinoma produce soluble factors that inhibit lymphocyte function. Furthermore, these experiments suggest that the inhibition previously observed with enzymatically disaggregated fresh tumors is due to factors produced by the tumor cells rather than by other cells within the tumor matrix.
头颈部癌患者的免疫抑制现象已得到充分认识。先前的研究表明,存在分级免疫抑制,且随着在更接近原发性肿瘤处测量淋巴细胞活性,这种抑制会变得更加明显。在新鲜肿瘤中,已鉴定出一种可溶性因子,它可能部分解释了观察到的分级免疫抑制现象。
研究头颈部鳞状细胞癌细胞系产生的可溶性因子对白细胞介素2、刀豆球蛋白A和植物血凝素诱导的淋巴因子激活的杀伤细胞细胞毒性及外周血淋巴细胞增殖的影响。
使用5种头颈部鳞状细胞癌细胞系,在4天的培养期内产生条件性上清液,并检测其抑制白细胞介素2、刀豆球蛋白A和植物血凝素诱导的淋巴因子激活的杀伤细胞细胞毒性及外周血幼稚淋巴细胞增殖的能力。
与对照组相比,所有条件性上清液均显著抑制了淋巴因子激活的杀伤细胞细胞毒性的产生,且这种抑制呈剂量依赖性。相比之下,髓性白血病肿瘤细胞系K562和卵巢上皮细胞系SKOV - 3的上清液未能抑制细胞毒性。头颈部鳞状细胞癌细胞系产生的条件性上清液也显著抑制了白细胞介素2、刀豆球蛋白A和植物血凝素诱导的外周血幼稚淋巴细胞增殖。
这些研究表明,头颈部鳞状细胞癌细胞系产生抑制淋巴细胞功能的可溶性因子。此外,这些实验表明,先前在酶解新鲜肿瘤中观察到的抑制作用是由于肿瘤细胞产生的因子,而非肿瘤基质中的其他细胞。