He Chaobin, Huang Xin, Zhang Yu, Lin Xiaojun, Li Shengping
Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.
Clin Transl Med. 2020 Jun;10(2):e39. doi: 10.1002/ctm2.39. Epub 2020 Jun 4.
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.
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.
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.
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.
不可逆电穿孔已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中的免疫变化，并探讨不可逆电穿孔（IRE）是否能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。
建立皮下和原位胰腺癌模型，用于评估IRE的免疫调节作用。在IRE前后的多个组织样本中评估T细胞的浸润情况。然后通过比较原位消融IRE后皮下肿瘤的生长情况或暴露于IRE处理的Pan02的肿瘤培养上清液（TSN）后的肿瘤生长情况来评估远隔效应。体外检测IRE后肿瘤细胞损伤相关分子模式（DAMPs）的表达。
IRE可显著抑制肿瘤生长并增加CD8 T细胞的浸润。在用IRE消融或用IRE处理的Pan02的TSN刺激后，未处理肿瘤的生长受到抑制，小鼠体内效应性CD8 T细胞和记忆T细胞显著增加。此外，肿瘤生长的抑制作用随着电穿孔强度水平的增加而增强。IRE通过增加DAMPs的合成和分泌诱导肿瘤细胞的ICD。
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不仅导致原位肿瘤完全消退，还诱导远隔效应，抑制潜在病变的生长。
