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放射治疗联合免疫治疗可改善小鼠黑色素瘤的免疫浸润并增强远隔效应。

Radiotherapy combined with immunotherapy could improve the immune infiltration of melanoma in mice and enhance the abscopal effect.

作者信息

Zheng Yufeng, Liu Xue, Li Na, Zhao Aimei, Sun Zhiqiang, Wang Meihua, Luo Judong

机构信息

Department of Radiotherapy, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, China.

Department of Radiotherapy, Dalian Medical University, Dalian, China.

出版信息

Radiat Oncol J. 2023 Jun;41(2):129-139. doi: 10.3857/roj.2023.00185. Epub 2023 Jun 29.

Abstract

PURPOSE

To analyze the gene mutation, immune infiltration and tumor growth of primary tumor and distant tumor under different treatment modes.

MATERIALS AND METHODS

Twenty B16 murine melanoma cells were injected subcutaneously into the of both sides of the thigh, simulating a primary tumor and a secondary tumor impacted by the abscopal effect, respectively. They were divided into blank control group, immunotherapy group, radiotherapy group, and radiotherapy combined immunotherapy group. During this period, tumor volume was measured, and RNA sequencing was performed on tumor samples after the test. R software was used to analyze differentially expressed genes, functional enrichment, and immune infiltration.

RESULTS

We found that any treatment mode could cause changes in differentially expressed genes, especially the combination treatment. The different therapeutic effects might be caused by gene expression. In addition, the proportions of infiltrating immune cells in the irradiated and abscopal tumors were different. In the combination treatment group, T-cell infiltration in the irradiated site was the most obvious. In the immunotherapy group, CD8+ T-cell infiltration in the abscopal tumor site was obvious, but immunotherapy alone might have a poor prognosis. Whether the irradiated or abscopal tumor was evaluated, radiotherapy combined with anti-programmed cell death protein 1 (anti-PD-1) therapy produced the most obvious tumor control and might have a positive impact on prognosis.

CONCLUSION

Combination therapy not only improves the immune microenvironment but may also have a positive impact on prognosis.

摘要

目的

分析不同治疗模式下原发性肿瘤和远处肿瘤的基因突变、免疫浸润及肿瘤生长情况。

材料与方法

将20个B16小鼠黑色素瘤细胞分别皮下注射到双侧大腿,分别模拟受远隔效应影响的原发性肿瘤和继发性肿瘤。将其分为空白对照组、免疫治疗组、放射治疗组和放射治疗联合免疫治疗组。在此期间,测量肿瘤体积,并在实验结束后对肿瘤样本进行RNA测序。使用R软件分析差异表达基因、功能富集和免疫浸润情况。

结果

我们发现任何治疗模式均可导致差异表达基因发生变化,尤其是联合治疗。不同的治疗效果可能由基因表达引起。此外,照射部位和远隔部位肿瘤中浸润免疫细胞的比例不同。联合治疗组中,照射部位T细胞浸润最为明显。免疫治疗组中,远隔部位肿瘤部位CD8 + T细胞浸润明显,但单纯免疫治疗可能预后较差。无论评估照射部位还是远隔部位肿瘤,放射治疗联合抗程序性细胞死亡蛋白1(抗PD - 1)治疗产生的肿瘤控制最为明显,可能对预后有积极影响。

结论

联合治疗不仅改善免疫微环境,而且可能对预后有积极影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e144/10326504/10ad550fef48/roj-2023-00185f1.jpg

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