Enhanced efficacy of direct immunochemotherapy for hepatic cancer with image-guided intratumoral radiofrequency hyperthermia.
Enhanced efficacy of direct immunochemotherapy for hepatic cancer with image-guided intratumoral radiofrequency hyperthermia.
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DOI：
10.1136/jitc-2022-005619
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发表时间：
2022-11
影响因子：
10.9
通讯作者：
中科院分区：
文献类型：
--
作者：
预防中大型肝细胞癌（HCC）射频消融（RFA）后肿瘤复发仍然是一个挑战。免疫化疗是免疫疗法与化疗的结合，已证明在增强某些恶性肿瘤的治疗效果方面具有巨大潜力。在这项研究中，我们验证了使用 LTX-315 射频热疗 (RFH) 增强瘤内免疫化疗联合脂质体阿霉素治疗大鼠原位 HCC 的可行性。不同组的荧光素酶标记的大鼠肝癌细胞和大鼠原位肝癌模型采用：（1）磷酸盐缓冲盐水； （2）RFH； (3)LTX-315； (4) RFH+LTX-315； (5)脂质体阿霉素； (6)RFH+脂质体阿霉素； (7)LTX-315+脂质体阿霉素； (8)RFH+LTX-315+脂质体阿霉素。比较不同处理组的细胞活力和凋亡。通过光学和超声成像量化肿瘤大小的变化，并通过随后的组织病理学证实。探讨了三联治疗（RFH+LTX-315+脂质体阿霉素）的潜在潜在生物学机制。流式细胞术和MTS测定显示，与其他七组相比，三联治疗组的凋亡细胞百分比最高，细胞活力最低（p<0.001）。与其他七组相比，该组肿瘤的生物发光信号强度下降最明显，肿瘤体积最小（p<0.001）。肿瘤中观察到 CD8+ T 细胞、CD8+/干扰素 (IFN)-γ+ T 细胞、CD8+/肿瘤坏死因子 (TNF)-α+ T 细胞和自然杀伤细胞显着增加，而调节性 T 细胞显着减少 (p<0.001)。同时，血浆（白细胞介素（IL）-2、IL-12、IL-18、IFN-γ）和肿瘤（IL-2、IL-18、IFN-γ、TNF-α）中的Th1型细胞因子水平显着升高，而血浆和肿瘤中的Th2型细胞因子IL-4和IL-10水平显着降低。瘤内RFA相关RFH可增强LTX-315联合脂质体阿霉素免疫化疗治疗HCC的疗效，这可能为提高中大型HCC热消融疗效提供新策略。
It is still a challenge to prevent tumor recurrence post radiofrequency ablation (RFA) of medium-to-large hepatocellular carcinomas (HCC). Immunochemotherapy, a combination of immunotherapy with chemotherapy, has demonstrated a great potential in augmenting the treatment efficacy for some malignancies. In this study, we validated the feasibility of using radiofrequency hyperthermia (RFH)-enhanced intratumoral immunochemotherapy of LTX-315 with liposomal doxorubicin for rat orthotopic HCC. Different groups of luciferase-labeled rat HCC cells and rat orthotopic HCC models were treated by: (1) phosphate buffered saline; (2) RFH; (3) LTX-315; (4) RFH+LTX-315; (5) liposomal doxorubicin; (6) RFH+liposomal doxorubicin; (7) LTX-315+liposomal doxorubicin; and (8) RFH+LTX-315+liposomal doxorubicin. Cell viabilities and apoptosis of different treatment groups were compared. Changes in tumor sizes were quantified by optical and ultrasound imaging, which were confirmed by subsequent histopathology. The potential underlying biological mechanisms of the triple combination treatment (RFH+LTX-315+liposomal doxorubicin) were explored. Flow cytometry and MTS assay showed the highest percentage of apoptotic cells and lowest cell viability in the triple combination treatment group compared with other seven groups (p<0.001). Tumors in this group also presented the most profound decrease in bioluminescence signal intensities and the smallest tumor volumes compared with other seven groups (p<0.001). A significant increase of CD8+ T cells, CD8+/interferon (IFN)-γ+ T cells, CD8+/tumor necrosis factor (TNF)-α+ T cells, and natural killer cells, and a significant decrease of regulatory T cells were observed in the tumors (p<0.001). Meanwhile, a significantly higher level of Th1-type cytokines in both plasma (interleukin (IL)-2, IL-12, IL-18, IFN-γ) and tumors (IL-2, IL-18, IFN-γ, TNF-α), as well as a significantly lower Th2-type cytokines of IL-4 and IL-10 in plasma and tumor were detected. Intratumoral RFA-associated RFH could enhance the efficacy of immunochemotherapy of LTX-315 with liposomal doxorubicin for HCC, which may provide a new strategy to increase the curative efficacy of thermal ablation for medium-to-large HCC.
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影响因子：
5.8
作者：
Camilio, Ketil Andre;Berge, Gerd;Ravuri, Chandra Sekhar;Rekdal, Oystein;Sveinbjornsson, Baldur
通讯作者：
Sveinbjornsson, Baldur
影响因子：
19.7
作者：
Shi, Yaoping;Zhang, Feng;Yang, Xiaoming
通讯作者：
Yang, Xiaoming
影响因子：
4.7
作者：
Qian K;Chen M;Zhang F;Chick JFB;Ji H;Zheng C;Yang X
通讯作者：
Yang X
影响因子：
7.2
作者：
Nestvold J;Wang MY;Camilio KA;Zinöcker S;Tjelle TE;Lindberg A;Haug BE;Kvalheim G;Sveinbjørnsson B;Rekdal Ø
通讯作者：
Rekdal Ø
影响因子：
4.6
作者：
Munoz, Nina M.;Dupuis, Crystal;Williams, Malea;Dixon, Katherine;McWatters, Amanda;Zhang, Jie;Pavuluri, Swathi;Rao, Arvind;Duda, Dan G.;Kaseb, Ahmed;Sheth, Rahul A.
通讯作者：
Sheth, Rahul A.