Kerrebijn J D, Simons P J, Tas M, Balm A J, Drexhage H A
Department of Otolaryngology Head and Neck Surgery, University Hospital Dijkzigt, Rotterdam, The Netherlands.
Eur Arch Otorhinolaryngol. 1995;252(7):409-16. doi: 10.1007/BF00167311.
Head and neck squamous cell carcinoma patients have been characterized by impairments in their cell-mediated immune system, particularly by decreased chemotactic function of monocytes and impairments in the function of the monocyte-derived dendritic cells (viz, a decreased capability to form cell "clusters"). These impairments are thought to be due to immunosuppressive factors of low molecular mass released by tumor, the so-called p15E-like factors. These suppressive effects of p15-like factors can be neutralized in vitro by thymic peptides, such as thymostimulin (TP1). In a randomized double-blind, placebo-controlled multicenter trial in the Netherlands, 41 patients with operable head and neck squamous cell carcinomas (HNSCC) were treated for 10 days prior to surgery with intramuscular TP1 in one of three dosages (0.5 mg/kg; 1.0 mg/kg or 2.0 mg/kg body weight) or treated with placebo. Assessment of monocyte chemotaxis, the capability of dendritic cells to form clusters and the presence of p15E-like low-molecular-mass factors (LMMFs) in serum was performed before TP1 treatment and on the day of surgery. Findings demonstrated that TP1 in a dose of 1.0 mg/kg and 2.0 mg/kg resulted in normalization of impaired monocyte chemotactic capability. Although the cluster capability of dendritic cells after TP1 treatment improved, values only reached statistical significance for the 0.5 mg/kg group. Serum p15E-like LMMF levels were not affected by TP1 treatment in any of the patient groups. Contrary to expectations we found no correlation between elevated immunosuppressive LMMFs and defective monocyte chemotaxis or cluster capability of dendritic cells. We conclude that treatment with TP1 can improve monocyte chemotaxis in HNSCC patients but an effect on the production of p15E-like factors by carcinoma cells could not be demonstrated.
头颈部鳞状细胞癌患者的特征是细胞介导的免疫系统受损，尤其是单核细胞趋化功能下降以及单核细胞衍生的树突状细胞功能受损（即形成细胞“簇”的能力下降）。这些损伤被认为是由于肿瘤释放的低分子量免疫抑制因子，即所谓的p15E样因子。p15样因子的这些抑制作用在体外可被胸腺肽（如胸腺刺激素（TP1））中和。在荷兰进行的一项随机双盲、安慰剂对照的多中心试验中，41例可手术的头颈部鳞状细胞癌（HNSCC）患者在手术前10天接受了三种剂量之一（0.5mg/kg；1.0mg/kg或2.0mg/kg体重）的肌肉注射TP1治疗，或接受安慰剂治疗。在TP1治疗前和手术当天，对单核细胞趋化性、树突状细胞形成簇的能力以及血清中p15E样低分子量因子（LMMF）的存在情况进行了评估。结果表明，1.0mg/kg和2.0mg/kg剂量的TP1可使受损的单核细胞趋化能力恢复正常。虽然TP1治疗后树突状细胞的簇形成能力有所改善，但仅0.5mg/kg组的值达到统计学意义。在任何患者组中，TP1治疗均未影响血清p15E样LMMF水平。与预期相反，我们发现免疫抑制性LMMF升高与单核细胞趋化性缺陷或树突状细胞的簇形成能力之间没有相关性。我们得出结论，TP1治疗可改善HNSCC患者的单核细胞趋化性，但未能证明其对癌细胞产生p15E样因子有影响。
