Konjević Gordana, Jović V, Radomirović Vesna, Spuzić I
Glas Srp Akad Nauka Med. 2002(47):121-36.
Malignant melanoma is well known for its poor response to chemotherapy, radiotherapy and its susceptibility to immunotherapy. Considering that dacarbazine (DTIC) and interferon alpha (IFNalpha) are among the most frequently used agents in the treatment of melanoma, the aim of this study was to evaluate the kinetics of immunological changes during adjuvant treatment of melanoma patients with DTIC or with IFNalpha monotherapy, as well as with their combination in metastatic disease. Pre-therapy values of immunological parameters showed significantly decreased NK cell activity, altered in vitro production of TNFalpha, IL-2 and proliferative response of peripheral blood lymphocytes (PBL), while percentage of PBL subpopulations was unchanged. During therapy, NK cell activity was significantly increased after the 1st cycle of combined chemoimmunotherapy (DTIC + IFNalpha), followed by a significant decrease after the 2nd cycle of therapy. Furthermore, in this group, there was a significant increase in CD4+ T helper cell percentage after the 1st cycle of therapy. Serial monitoring of activation antigens also showed a significant increase in the expression of CD38 on CD8+ cytotoxic T cells, after the 1st and 2nd cycle in combined chemoimmunotherapy group and, after 30 days, in the group of patients treated with IFNalpha, only. The increase in the expression of HLA-DR activation antigen on CD3+ and CD8+ T cells had a gradual increase and significant rise after the 2nd cycle of combine chemoimmunotherapy, only. The dynamic of immunological changes, mostly observed in combined chemoimmunotherapy, and rarely in IFNalpha monotherapy gives valuable insight into induced immunomodulation, suggesting early, but transient favourable changes, that could be prolonged by timely introduction of other immunotherapeutic agents.
恶性黑色素瘤以其对化疗、放疗反应不佳以及对免疫疗法敏感而闻名。鉴于达卡巴嗪(DTIC)和干扰素α(IFNα)是治疗黑色素瘤最常用的药物,本研究的目的是评估黑色素瘤患者接受DTIC或IFNα单药辅助治疗以及二者联合用于转移性疾病治疗期间免疫变化的动力学。免疫参数的治疗前值显示自然杀伤(NK)细胞活性显著降低,肿瘤坏死因子α(TNFα)、白细胞介素-2(IL-2)的体外产生以及外周血淋巴细胞(PBL)的增殖反应发生改变,而PBL亚群的百分比未变。治疗期间,联合化疗免疫疗法(DTIC + IFNα)第1周期后NK细胞活性显著增加,随后在第2周期治疗后显著降低。此外,在该组中,治疗第1周期后CD4 + T辅助细胞百分比显著增加。对激活抗原的连续监测还显示,联合化疗免疫疗法组第1和第2周期后,以及仅接受IFNα治疗的患者组在30天后,CD8 + 细胞毒性T细胞上CD38的表达显著增加。仅在联合化疗免疫疗法第2周期后,CD3 + 和CD8 + T细胞上HLA-DR激活抗原的表达呈逐渐增加并显著升高。免疫变化的动态情况,大多在联合化疗免疫疗法中观察到,而在IFNα单药治疗中很少见,这为诱导的免疫调节提供了有价值的见解,表明存在早期但短暂的有利变化,可通过及时引入其他免疫治疗药物来延长。