基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
过继性自然杀伤(NK)细胞疗法是治疗三阴性乳腺癌的一种有前景的策略,但其疗效往往受到瘤内持久性差以及在免疫抑制性肿瘤微环境中功能耗竭的限制。
英文原题:Prospective Evaluation of Immune Activation Associated with Response to Radioembolization Assessed with PET/CT in Women with Breast Cancer Liver Metastasis.
在基线和TARE后1-2个月收集外周血和肝肿瘤活检样本。
背景 乳腺癌肝转移(BCLM)经动脉放射性栓塞(TARE)对 antitumor 免疫的影响尚不明确,这阻碍了 TARE 最佳候选者的选择。目的 确定 BCLM 参与者中 TARE 在 PET/CT 上的缓解是否与特定免疫标志物(细胞因子和免疫细胞群体)相关。材料与方法 这项前瞻性初步研究纳入了 23 名计划接受 TARE 的 BCLM 女性(2018 年 6 月至 2020 年 2 月)。在基线和 TARE 后 1-2 个月收集外周血和肝肿瘤活检标本。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TIL(肿瘤浸润淋巴细胞)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。使用实体肿瘤 PET 缓解标准(修改版)确定治疗组织的完全缓解(CR)。对数转换后,使用配对 t 检验比较 TARE 前后的免疫标志物水平。使用 Wilcoxon 秩和检验或非配对 t 检验评估与 CR 的相关性。结果 纳入 20 名女性。TARE 后,外周 IL-6(几何均值,1.0 vs 1.6 pg/mL;P = .02)、IL-10(0.2 vs 0.4 pg/mL;P = .001)和 IL-15(1.9 vs 2.4 pg/mL;P = .01)升高。在活检组织中,淋巴细胞活化基因 3 阳性 CD4+ TIL 增加(15% vs 31%;P < .001)。20 名参与者中有 8 名(40% [精确 95% CI:19,64])达到 CR。达到 CR 的参与者在流式细胞术下基线外周单核细胞较低(10% vs 29%;P < .001)和 MDSC 较低(1% vs 5%;P < .001),程序性细胞死亡蛋白(PD)1 阳性 CD4+ TIL 较高(59% vs 26%;P = .006),并且肿瘤中 PD-1+ 染色较高(2% vs 1%;P = .046)。结论 对经动脉放射栓塞的完全缓解与较低的基线细胞因子、单核细胞和髓源性抑制细胞水平以及较高的程序性细胞死亡蛋白1阳性TIL(肿瘤浸润淋巴细胞)水平相关。RSNA,2022 本文提供在线补充材料。
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.
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