Th1 adjuvant ARNAX, in combination with radiation therapy, enhances tumor regression in mouse tumor-implant models.

IF 3.3 4区 医学 Q3 IMMUNOLOGY Immunology letters Pub Date : 2024-11-25 DOI:10.1016/j.imlet.2024.106947
Aya Miyazaki, Sumito Yoshida, Yohei Takeda, Utano Tomaru, Misako Matsumoto, Tsukasa Seya
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引用次数: 0

Abstract

Radiation therapy (RT) rarely induces tumor regression at untreated metastatic sites, the so-called abscopal effect. A syngeneic tumor (EG7) transplanted into a Th1-dominant mouse strain (C57BL/6) regressed significantly on the treated side and less on the contralateral side after RT. Additional subcutaneous administration of ARNAX, a non-inflammatory adjuvant, further accelerated tumor regression on the untreated side. This suggests that ARNAX after RT significantly enhances the tumor regression effect on the irrelevant tumor. Based on this setting, we next observed similar tumor shrinkage after RT and ARNAX by transplanting syngeneic breast cancer tumors (4T1) into a Th2-dominant mouse strain (BALB/c). The results were as follows: 1. ARNAX enhanced RT-mediated tumor shrinkage comparable to polyI:C; 2. In the Th2 mouse strain, little tumor regression occurred on the untreated side compared to tumor regression on the treated side after RT alone; 3. RT+ARNAX treatment caused additive regression on the treated side and induced slight tumor regression on the untreated side; 4. PD-L1 antibody + RT combination therapy caused tumor regression and further induced additive regression with ARNAX; 5. The combination of RT and ARNAX reduced the number and volume of lung metastases compared to RT alone. However, tumor regression was not always accompanied by a significant prolongation of survival in the mice receiving our regimen and protocol (one 10Gy radiation and a single ARNAX treatment). In conclusion, RT therapy promoted abscopal tumor regression in both Th2 and Th1 models with the addition of the non-inflammatory adjuvant ARNAX.

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Th1辅助剂ARNAX与放射治疗相结合,可增强小鼠肿瘤植入模型中肿瘤的消退。
放射治疗(RT)很少能诱导未经治疗的转移部位的肿瘤消退,即所谓的缺席效应。将合成肿瘤(EG7)移植到 Th1 显性小鼠品系(C57BL/6)中,RT 治疗后,治疗侧肿瘤消退明显,而对侧则消退较少。额外皮下注射非炎性辅助剂 ARNAX 进一步加速了未治疗侧的肿瘤消退。这表明,RT 后给予 ARNAX 能显著增强无关肿瘤的消退效果。在此基础上,我们接下来通过将合成乳腺癌肿瘤(4T1)移植到 Th2 显性小鼠品系(BALB/c)中,观察到 RT 和 ARNAX 治疗后类似的肿瘤缩小情况。结果如下:1.ARNAX增强了RT介导的肿瘤缩小,其效果与polyI:C相当;2.在Th2小鼠品系中,与单独RT治疗后治疗侧的肿瘤缩小相比,未治疗侧的肿瘤缩小很小;3.RT+ARNAX治疗使治疗侧的肿瘤缩小相加,并诱导未治疗侧的肿瘤轻微缩小;4.PD-L1抗体+RT联合治疗使治疗侧的肿瘤缩小相加,并诱导未治疗侧的肿瘤轻微缩小。4. PD-L1 抗体+RT联合疗法可使肿瘤消退,并进一步诱导 ARNAX 的相加消退;5. 与单独使用 RT 相比,RT 和 ARNAX 联合疗法可减少肺转移灶的数量和体积。然而,在接受我们的方案(一次 10Gy 放射治疗和一次 ARNAX 治疗)的小鼠中,肿瘤消退并不总是伴随着生存期的显著延长。总之,在Th2和Th1模型中,RT疗法在添加非炎性辅助剂ARNAX后都能促进肿瘤的消退。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Immunology letters
Immunology letters 医学-免疫学
CiteScore
7.60
自引率
0.00%
发文量
86
审稿时长
44 days
期刊介绍: Immunology Letters provides a vehicle for the speedy publication of experimental papers, (mini)Reviews and Letters to the Editor addressing all aspects of molecular and cellular immunology. The essential criteria for publication will be clarity, experimental soundness and novelty. Results contradictory to current accepted thinking or ideas divergent from actual dogmas will be considered for publication provided that they are based on solid experimental findings. Preference will be given to papers of immediate importance to other investigators, either by their experimental data, new ideas or new methodology. Scientific correspondence to the Editor-in-Chief related to the published papers may also be accepted provided that they are short and scientifically relevant to the papers mentioned, in order to provide a continuing forum for discussion.
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