放疗期间同步给予顺铂与单纯放疗对子宫颈癌患者免疫功能的影响。

Effects of concurrent cisplatinum administration during radiotherapy vs. radiotherapy alone on the immune function of patients with cancer of the uterine cervix.

作者信息

Santin A D, Hermonat P L, Ravaggi A, Bellone S, Roman J, Pecorelli S, Cannon M, Parham G P

机构信息

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Arkansas for Medical Sciences, Little Rock, AR 72205-7199, USA.

出版信息

Int J Radiat Oncol Biol Phys. 2000 Nov 1;48(4):997-1006. doi: 10.1016/s0360-3016(00)00769-0.

DOI:10.1016/s0360-3016(00)00769-0

PMID:11072156

Abstract

PURPOSE

To compare the effects of concurrent administration of cisplatinum (40 mg/m(2)/weekly) with radiation therapy (C-RT) to those induced by radiation therapy alone (RT) on the immune function of patients with locally advanced cervical cancer.

METHODS AND MATERIALS

In 8 prospectively randomized patients (i.e., 4 receiving RT vs. 4 receiving C-RT), lymphocyte populations including CD3+, CD4+ and CD8+ T-cell subsets, B cells (CD19+) and natural killer cells (CD56+, CD16+, CD3-) were studied before, during, and after therapy. Expression of the activation marker CD25 on CD3+ T cells, intracellular levels of perforin in CD8+ and CD56+ cells, and interferon-gamma (IFN-gamma) and IL-2 in CD4+ and CD8+ T cells was also measured. Finally, lymphoblast transformation and natural killer (NK) cytotoxic activity were assessed.

RESULTS

Both RT and C-RT significantly decreased the mean absolute number of all lymphocyte subsets compared to pretreatment levels (p > 0.001). However, no differences were detected in the characteristics or the magnitude of the lymphopenia induced by the two treatments. Both RT and C-RT increased similarly the percentages of CD25-positive lymphocytes (p > 0.001), and significantly decreased PHA-induced T-cell lymphoblast transformation (p > 0.001) and NK cytotoxic activity against K562 cells (p > 0.001). The percentage of perforin-positive and CD8+ T cells was not altered during either treatment, whereas the percentage of perforin-positive and CD56+ cells was significantly reduced during both treatments, and correlated with reduced cytotoxicity against K562 cells. The percentages of CD8+ IFN-gamma+ and CD4+ IFN-gamma+ T cells as well as that of CD8+ IL-2+ and CD4+ IL2+ T cells were not significantly altered by C-RT compared to RT alone. Finally, with both regimens, NK cells and B-cell numbers showed a more rapid recovery than T-cell numbers.

CONCLUSION

Administration of concurrent cisplatinum to radiation may synergistically increase cytotoxic effects of radiation on tumor cells but does not alter the magnitude and the characteristics of radiation-induced immunosuppression.

摘要

目的

比较顺铂（40mg/m²/周）与放射治疗同步进行（C-RT）和单纯放射治疗（RT）对局部晚期宫颈癌患者免疫功能的影响。

方法和材料

8例前瞻性随机分组患者（即4例接受RT，4例接受C-RT），在治疗前、治疗期间和治疗后研究淋巴细胞群体，包括CD3⁺、CD4⁺和CD8⁺T细胞亚群、B细胞（CD19⁺）和自然杀伤细胞（CD56⁺、CD16⁺、CD3⁻）。还检测了CD3⁺T细胞上激活标志物CD25的表达、CD8⁺和CD56⁺细胞中穿孔素的细胞内水平以及CD4⁺和CD8⁺T细胞中干扰素-γ（IFN-γ）和IL-2的水平。最后，评估淋巴细胞转化和自然杀伤（NK）细胞毒性活性。

结果

与治疗前水平相比，RT和C-RT均显著降低了所有淋巴细胞亚群的平均绝对数量（p＞0.001）。然而，两种治疗引起的淋巴细胞减少的特征或程度未检测到差异。RT和C-RT均同样增加了CD25阳性淋巴细胞的百分比（p＞0.001），并显著降低了PHA诱导的T细胞淋巴细胞转化（p＞0.001）和对K562细胞的NK细胞毒性活性（p＞0.001）。在两种治疗期间，穿孔素阳性和CD8⁺T细胞的百分比均未改变，而在两种治疗期间，穿孔素阳性和CD56⁺细胞的百分比均显著降低，且与对K562细胞的细胞毒性降低相关。与单纯RT相比，C-RT对CD8⁺IFN-γ⁺和CD4⁺IFN-γ⁺T细胞的百分比以及CD8⁺IL-2⁺和CD4⁺IL-2⁺T细胞的百分比均无显著改变。最后，两种方案中，NK细胞和B细胞数量的恢复均比T细胞数量更快。