Microwave ablation enhances tumor-specific immune response in patients with hepatocellular carcinoma.
Microwave ablation enhances tumor-specific immune response in patients with hepatocellular carcinoma.
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DOI：
10.1007/s00262-020-02734-1
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Schlößer HA
中科院分区：
文献类型：
--
作者：
Leuchte K;Staib E;Thelen M;Gödel P;Lechner A;Zentis P;Garcia-Marquez M;Waldschmidt D;Datta RR;Wahba R;Wybranski C;Zander T;Quaas A;Drebber U;Stippel DL;Bruns C;von Bergwelt-Baildon M;Wennhold K;Schlößer HA
热消融疗法是局部肝细胞癌（HCC）的标准治疗方法。除局部肿瘤破坏外，消融还导致远端病变的远端效应，最可能由抗肿瘤免疫应答介导。虽然微波消融（MWA）正在逐渐取代其他消融技术，但其全身免疫刺激作用的研究很少。我们分析了热消融后肝癌患者外周血中的肿瘤特异性免疫反应，以及T细胞反应和疾病结局。虽然在前瞻性患者队列（n = 23）的连续样本中进行的全面流式细胞术分析表明MWA对循环免疫细胞亚群的影响仅为中度，但针对7种肿瘤相关抗原（TTA）的特异性T细胞应答的荧光点分析显示，30%的患者出现新发或增强的肿瘤特异性免疫应答。这种抗肿瘤免疫应答与肿瘤控制相关，因为针对TAA的干扰素-γ和白细胞介素-5 T细胞应答在长期缓解的患者中更常见MWA后（> 1年）（7/16）与早期复发患者相比（0/13名患者）和肿瘤特异性T细胞应答（IFN-γ和/或IL-5）的存在与更长的无进展生存期（27.5个月对10.0个月）相关。对接受MWA和切除联合治疗的患者的化学染色存档HCC样本（n = 18）进行数字图像分析，显示热消融时T细胞丰度高的患者的无病生存率上级（37.4 vs 13.1个月）。我们的数据表明MWA在HCC患者中具有显著的免疫相关作用，并为局部消融和免疫治疗在这种具有挑战性的疾病中的组合提供了额外的证据。本文的在线版本（10.1007/s 00262 -020-02734-1）包含补充材料，可供授权用户使用。
Thermal ablative therapies are standard treatments for localized hepatocellular carcinoma (HCC). In addition to local tumor destruction, ablation leads to abscopal effects in distant lesions most likely mediated by an anti-tumor immune response. Although microwave ablation (MWA) is increasingly substituting other ablative techniques, its systemic immunostimulatory effects are poorly studied. We analyzed tumor-specific immune responses in peripheral blood of HCC patients after thermal ablation with regard to T cell responses and disease outcome. While comprehensive flow cytometric analyses in sequential samples of a prospective patient cohort (n = 23) demonstrated only moderate effects of MWA on circulating immune cell subsets, fluorospot analyses of specific T cell responses against seven tumor-associated antigens (TTAs) revealed de-novo or enhanced tumor-specific immune responses in 30% of patients. This anti-tumor immune response was related to tumor control as Interferon-y and Interleukin-5 T cell responses against TAAs were more frequent in patients with a long-time remission (> 1 year) after MWA (7/16) compared to patients suffering from an early relapse (0/13 patients) and presence of tumor-specific T cell response (IFN-y and/or IL-5) was associated to longer progression-free survival (27.5 vs. 10.0 months). Digital image analysis of immunohistochemically stained archival HCC samples (n = 18) of patients receiving combined MWA and resection revealed a superior disease-free survival of patients with high T cell abundance at the time of thermal ablation (37.4 vs. 13.1 months). Our data demonstrates remarkable immune-related effects of MWA in HCC patients and provides additional evidence for a combination of local ablation and immunotherapy in this challenging disease. The online version of this article (10.1007/s00262-020-02734-1) contains supplementary material, which is available to authorized users.
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影响因子：
64.8
作者：
Helmink BA;Reddy SM;Gao J;Zhang S;Basar R;Thakur R;Yizhak K;Sade-Feldman M;Blando J;Han G;Gopalakrishnan V;Xi Y;Zhao H;Amaria RN;Tawbi HA;Cogdill AP;Liu W;LeBleu VS;Kugeratski FG;Patel S;Davies MA;Hwu P;Lee JE;Gershenwald JE;Lucci A;Arora R;Woodman S;Keung EZ;Gaudreau PO;Reuben A;Spencer CN;Burton EM;Haydu LE;Lazar AJ;Zapassodi R;Hudgens CW;Ledesma DA;Ong S;Bailey M;Warren S;Rao D;Krijgsman O;Rozeman EA;Peeper D;Blank CU;Schumacher TN;Butterfield LH;Zelazowska MA;McBride KM;Kalluri R;Allison J;Petitprez F;Fridman WH;Sautès-Fridman C;Hacohen N;Rezvani K;Sharma P;Tetzlaff MT;Wang L;Wargo JA
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Wargo JA
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3.1
作者：
Chen, Zubing;Shen, Shiqiang;Tao, Jianpin
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Tao, Jianpin
影响因子：
3.1
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Dong, BW;Zhang, J;Yu, G
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Yu, G
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2
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Mehta A;Oklu R;Sheth RA
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Sheth RA
影响因子：
10.1
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通讯作者：
He AR