Nouri A M, Hyde R, Oliver R T
Department of Oncology, Royal London Hospital, UK.
Cancer Immunol Immunother. 1994 Jul;39(1):68-70. doi: 10.1007/BF01517183.
Using immunocytochemical techniques the pattern of T cell markers and MHC antigens on peripheral blood mononuclear cells, and tumour biopsies of patients with superficial bladder cancer before and after intravesical human recombinant interleukin-2 (rhuIL-2) therapy (three cases at 1 MIU, four cases at 18 MIU and two cases at 54 MIU), was investigated. There was a slight but significant increase in the total number of circulating leucocytes, harvested from blood using density gradient technique, after intravesical rhuIL-2 treatment. Thus the mean +/- SD of seven cases before and after (more than 30 days of) IL-2 were 1.24 +/- 0.32 x 10(9)/l and 1.50 +/- 0.46 x 10(9)/l respectively (t-test, P = 0.032). However, this was substantially less than in samples collected after subcutaneously (six cases) and intravenously (seven cases) administering rhuIL-2, the results of which were 1.09 +/- 0.46 x 10(9)/l versus 2.22 +/- 0.68 x 10(9)/l (P = 0.016) and 0.84 x 10(9)/l versus 2.3 x 10(9)/l (P = 0.004) respectively. There was no demonstrable alteration in the percentage of cells positive for CD3, CD4, CD8, CD25 or CD56 in peripheral blood or urine populations in six patients treated with intravesical IL-2, or the pattern of MHC class I or II expression on tumour biopsies before and after treatment. Though this could have been a reflection of the fact that most of the cases had normal class I expression, there was one tumour with complete loss and one tumour with very low expression among the three cases showing stroma positivity for HLA-A3 antigens. Neither of these was altered by IL-2 treatment, nor was class II antigen expression, which was positive in five of nine cases before treatment. Given the lack of the expected major immunological changes and the poor clinical responses (one of nine complete responses lasted 3 months), it is concluded that the schedule has not produced an adequate dose intensity to induce lymphocyte activation and alternative schedules based on those developed from systemic treatment need exploration.
运用免疫细胞化学技术，对浅表性膀胱癌患者膀胱内注射重组人白细胞介素-2（rhuIL-2）治疗前后外周血单个核细胞以及肿瘤活检组织中的T细胞标志物和MHC抗原模式进行了研究（1 MIU剂量组3例、18 MIU剂量组4例、54 MIU剂量组2例）。膀胱内注射rhuIL-2治疗后，采用密度梯度技术从血液中采集的循环白细胞总数略有但显著增加。因此，7例患者在IL-2治疗前后（超过30天）的平均值±标准差分别为1.24±0.32×10⁹/L和1.50±0.46×10⁹/L（t检验，P = 0.032）。然而，这一数值显著低于皮下注射（6例）和静脉注射（7例）rhuIL-2后采集样本中的数值，皮下注射组的结果为1.09±0.46×10⁹/L对2.22±0.68×10⁹/L（P = 0.016），静脉注射组的结果为0.84×10⁹/L对2.3×10⁹/L（P = 0.004）。在6例接受膀胱内IL-2治疗的患者中，外周血或尿液中CD3、CD4、CD8、CD25或CD56阳性细胞百分比，以及治疗前后肿瘤活检组织中MHC I类或II类表达模式均无明显改变。尽管这可能反映了大多数病例I类表达正常这一事实，但在3例显示HLA - A3抗原基质阳性的病例中，有1例肿瘤完全缺失I类表达，1例肿瘤I类表达极低。IL-2治疗对这两者均无改变，II类抗原表达也未改变，治疗前9例中有5例呈阳性。鉴于缺乏预期的主要免疫变化以及临床反应不佳（9例完全缓解中有1例持续3个月），得出的结论是，该方案未产生足以诱导淋巴细胞激活的足够剂量强度，需要探索基于全身治疗方案制定的替代方案。
