Background

The impact of transarterial radioembolization (TARE) of breast cancer liver metastasis (BCLM) on antitumor immunity is unknown, which hinders the optimal selection of candidates for TARE.

Purpose

To determine whether response to TARE at PET/CT in participants with BCLM is associated with specific immune markers (cytokines and immune cell populations).

Materials and Methods

This prospective pilot study enrolled 23 women with BCLM who planned to undergo TARE (June 2018 to February 2020). Peripheral blood and liver tumor biopsies were collected at baseline and 1–2 months after TARE. Monocyte, myeloid-derived suppressor cell (MDSC), interleukin (IL), and tumor-infiltrating lymphocyte (TIL) levels were assessed with use of gene expression studies and flow cytometry, and immune checkpoint and cell surface marker levels with immunohistochemistry. Modified PET Response Criteria in Solid Tumors was used to determine complete response (CR) in treated tissue. After log-transformation, immune marker levels before and after TARE were compared using paired t tests. Association with CR was assessed with Wilcoxon rank-sum or unpaired t tests.

Results

Twenty women were included. After TARE, peripheral IL-6 (geometric mean, 1.0 vs 1.6 pg/mL; P = .02), IL-10 (0.2 vs 0.4 pg/mL; P = .001), and IL-15 (1.9 vs 2.4 pg/mL; P = .01) increased. In biopsy tissue, lymphocyte activation gene 3–positive CD4+ TILs (15% vs 31%; P < .001) increased. Eight of 20 participants (40% [exact 95% CI: 19, 64]) achieved CR. Participants with CR had lower baseline peripheral monocytes (10% vs 29%; P < .001) and MDSCs (1% vs 5%; P < .001) and higher programmed cell death protein (PD) 1–positive CD4+ TILs (59% vs 26%; P = .006) at flow cytometry and higher PD-1+ staining in tumor (2% vs 1%; P = .046).

Conclusion

Complete response to transarterial radioembolization was associated with lower baseline cytokine, monocyte, and myeloid-derived suppressor cell levels and higher programmed cell death protein 1–positive tumor-infiltrating lymphocyte levels.

© RSNA, 2022

Online supplemental material is available for this article.

中文翻译：

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在患有乳腺癌肝转移的女性中使用 PET/CT 评估与放射栓塞反应相关的免疫激活的前瞻性评估

背景

乳腺癌肝转移 (BCLM) 经动脉放射栓塞 (TARE) 对抗肿瘤免疫的影响尚不清楚，这阻碍了 TARE 候选者的最佳选择。

目的

确定 BCLM 参与者在 PET/CT 上对 TARE 的反应是否与特定免疫标志物（细胞因子和免疫细胞群）相关。

材料和方法

这项前瞻性试点研究招募了 23 名计划接受 TARE（2018 年 6 月至 2020 年 2 月）的 BCLM 女性。在基线和 TARE 后 1-2 个月收集外周血和肝肿瘤活检。使用基因表达研究和流式细胞术评估单核细胞、髓源性抑制细胞 (MDSC)、白细胞介素 (IL) 和肿瘤浸润淋巴细胞 (TIL) 水平，并使用免疫组织化学评估免疫检查点和细胞表面标志物水平。修改后的实体瘤 PET 反应标准用于确定治疗组织的完全反应 (CR)。对数转换后，使用配对t检验比较 TARE 前后的免疫标记物水平。使用 Wilcoxon 秩和或非配对t检验评估与 CR 的关联。

结果

其中包括 20 名女性。TARE 后，外周 IL-6（几何平均值，1.0 对 1.6 pg/mL；P = .02）、IL-10（0.2 对 0.4 pg/mL；P = .001）和 IL-15（1.9 对 2.4 pg /mL；P = .01) 增加。在活检组织中，淋巴细胞激活基因 3 阳性 CD4+ TIL（15% 对 31%；P < .001）增加。20 名参与者中有 8 名（40% [精确 95% CI：19、64]）达到 CR。CR 参与者的基线外周单核细胞（10% 对 29%；P < .001）和 MDSC（1% 对 5%；P < .001）和程序性细胞死亡蛋白 (PD) 1 阳性 CD4+ TIL 较高（59 % vs 26%；P = .006) 在流式细胞术中和肿瘤中更高的 PD-1+ 染色（2% vs 1%；P = .046）。

结论

对经动脉放射栓塞术的完全反应与较低的基线细胞因子、单核细胞和骨髓来源的抑制细胞水平以及较高的程序性细胞死亡蛋白 1 阳性肿瘤浸润淋巴细胞水平相关。

©北美放射学会，2022

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