T-cell activation and immune memory enhancement induced by irreversible electroporation in pancreatic cancer
T-cell activation and immune memory enhancement induced by irreversible electroporation in pancreatic cancer
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DOI：
10.1002/ctm2.39
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发表时间：
2020-06-04
影响因子：
10.6
通讯作者：
Li, Shengping
中科院分区：
文献类型：
--
作者：
He, Chaobin;Huang, Xin;Li, Shengping
背景不可逆电穿孔被证明可诱导胰腺癌的免疫变化，但仍缺乏组织学证据。本研究的目的是展示组织学上的免疫变化，并探讨不可逆电穿孔（IRE）是否可以诱导肿瘤细胞的免疫原性细胞死亡（ICD）并激活特异性免疫反应。方法建立皮下和原位胰腺癌模型并用于评估IRE的免疫调节效果。在 IRE 之前和之后评估了几个组织样本中 T 细胞的浸润。然后通过比较 IRE 原位消融或暴露于 IRE 处理的 Pan02 的肿瘤培养上清液 (TSN) 后皮下肿瘤的肿瘤生长来评估远隔效应。体外检测IRE后肿瘤细胞损伤相关分子模式(DAMPs)的表达。结果IRE能显着抑制肿瘤生长，增加CD8(+) T细胞的浸润。 IRE消融或经IRE处理的Pan02的TSN刺激后，未处理肿瘤的生长受到抑制，效应CD8(+) T细胞和记忆T细胞在小鼠中显着增加。此外，随着电穿孔强度的增加，肿瘤生长的抑制作用也增强。 IRE通过增加DAMPs的合成和分泌诱导肿瘤细胞的ICD。结论IRE通过增加特异性T细胞浸润诱导局部免疫调节。通过增强特异性免疫记忆，IRE不仅使肿瘤完全消退，而且还诱导远隔效应，抑制潜伏病灶的生长。
Background Irreversible electroporation is shown to induce immune changes in pancreatic cancer while the histology evidences are still lacking. The aim of this study is to show the immune changes in histology and explore whether irreversible electroporation (IRE) can induce immunogenic cell death (ICD) of tumor cells and activate specific immune responses.Methods Subcutaneous and orthotopic pancreatic cancer models were established and used to evaluate the effect of immune modulation of IRE. The infiltration of T cells was assessed in several tissue samples before and after IRE. Abscopal effect was then assessed by comparing the tumor growth of subcutaneous tumors after in situ ablation with IRE or exposure to tumor culture supernatant (TSN) of IRE-treated Pan02. The expression of damage-associated molecular patterns (DAMPs) of tumor cells after IRE was detected in vitro.Results IRE could significantly suppress the tumor growth and increase the infiltration of CD8(+) T cells. After ablation with IRE or stimulation with TSN of Pan02 treated by IRE, the growth of untreated tumor was suppressed and the effector CD8(+) T cells and memory T cells increased significantly in mice. Additionally, the inhibition effect of tumor growth increased along with the increasing strength levels of electroporation. IRE induced ICD of tumor cells by increasing the synthesis and secretion of DAMPs.Conclusions IRE induced local immunomodulation by increasing specific T cells infiltration. Through enhancing specific immune memory, IRE not only led a complete tumor regression in suit, but also induced abscopal effect, suppressing the growth of the latent lesions.