Jürgenliemk-Schulz I M, Renes I B, Rutgers D H, Everse L A, Bernsen M R, Den Otter W, Battermann J J
Department of Radiotherapy, University Hospital Utrecht, The Netherlands.
Radiat Oncol Investig. 1997;5(2):54-61. doi: 10.1002/(SICI)1520-6823(1997)5:2<54::AID-ROI3>3.0.CO;2-I.
The aim of this work was to improve radiotherapy results by immune stimulation. We tested the effects of a combination of radio- and immunotherapy, i.e., local low dose recombinant interleukin-2 (rIL-2) treatment, in two murine tumor models. Syngeneic tumors (SL2 lymphoma or M8013 mammary carcinoma) were induced subcutaneously on one or both flanks of mice. Irradiation was given either as a single dose (20 Gy) or fractionated (25 Gy) in 2 weeks. One or two cycles of rIL-2 were given concurrent with or subsequent to radiotherapy. One cycle of rIL-2 consisted of peritumoral injections administered on 5 consecutive days. Treatment effects were measured in terms of local tumor response and disease-free survival (DFS). The combined treatment modality was significantly better than treatment with either irradiation alone or rIL-2 alone. When tumors were inoculated on both flanks of the mice, combined radioimmunotherapy of one of the tumors also resulted in regression of the contralateral untreated tumor, indicating that a systemic anti-tumor immune reaction was induced. Additional rIL-2 injections did not enhance radiation toxicity. In conclusion supplementing irradiation with locally administered low doses of rIL-2 results in better local anti-tumor responses and DFS rates than either treatment alone without enhanced treatment toxicity. Furthermore, the local treatment induces a systemic anti-tumor reaction, influencing the growth patterns of a second, untreated tumor.
这项工作的目的是通过免疫刺激来改善放射治疗效果。我们在两种小鼠肿瘤模型中测试了放疗与免疫治疗联合的效果，即局部低剂量重组白细胞介素-2（rIL-2）治疗。在小鼠的一侧或两侧皮下诱导同基因肿瘤（SL2淋巴瘤或M8013乳腺癌）。照射采用单次剂量（20 Gy）或在2周内分次给予（25 Gy）。在放疗期间或放疗后给予一或两个周期的rIL-2。一个周期的rIL-2包括连续5天进行瘤周注射。根据局部肿瘤反应和无病生存期（DFS）来衡量治疗效果。联合治疗方式明显优于单纯放疗或单纯rIL-2治疗。当在小鼠两侧接种肿瘤时，对其中一个肿瘤进行联合放射免疫治疗也导致对侧未治疗肿瘤消退，表明诱导了全身性抗肿瘤免疫反应。额外的rIL-2注射并未增强放射毒性。总之，与单独的任何一种治疗相比，用局部给予的低剂量rIL-2补充照射可产生更好的局部抗肿瘤反应和DFS率，且不会增强治疗毒性。此外，局部治疗可诱导全身性抗肿瘤反应，影响第二个未治疗肿瘤的生长模式。
