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术中放疗在胰腺手术后诱导免疫反应活性。

Intraoperative radiation therapy induces immune response activity after pancreatic surgery.

机构信息

Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, 20, Eonju-ro 63 gil, Gangnam-gu, Seoul, 06229, South Korea.

Brain Korea 21 FOUR Project for Medical Science, Yonsei University, Seoul, South Korea.

出版信息

BMC Cancer. 2021 Oct 12;21(1):1097. doi: 10.1186/s12885-021-08807-3.

DOI:10.1186/s12885-021-08807-3
PMID:34641806
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8507125/
Abstract

BACKGROUND

Pancreatic cancer has highly aggressive features, such as local recurrence that leads to significantly high morbidity and mortality and recurrence after successful tumour resection. Intraoperative radiation therapy (IORT), which delivers targeted radiation to a tumour bed, is known to reduce local recurrence by directly killing tumour cells and modifying the tumour microenvironment.

METHODS

Among 30 patients diagnosed with pancreatic cancer, 17 patients received IORT immediately after surgical resection. We investigated changes in the immune response induced by IORT by analysing the peritoneal fluid (PF) and blood of patients with and without IORT treatment after pancreatic cancer surgery. Further, we treated three pancreatic cell lines with PF to observe proliferation and activity changes.

RESULTS

Levels of cytokines involved in the PI3K/SMAD pathway were increased in the PF of IORT-treated patients. Moreover, IORT-treated PF inhibited the growth, migration, and invasiveness of pancreatic cancer cells. Changes in lymphocyte populations in the blood of IORT-treated patients indicated an increased immune response.

CONCLUSIONS

Based on the characterisation and quantification of immune cells in the blood and cytokine levels in the PF, we conclude that IORT induced an anti-tumour effect by activating the immune response, which may prevent pancreatic cancer recurrence.

CLINICAL TRIAL REGISTRATION

NCT03273374 .

摘要

背景

胰腺癌具有侵袭性强的特点,如局部复发,导致发病率和死亡率显著升高,且肿瘤切除后也容易复发。术中放疗(IORT)通过向肿瘤床提供靶向放疗,已知可通过直接杀死肿瘤细胞和改变肿瘤微环境来降低局部复发率。

方法

在 30 名被诊断为胰腺癌的患者中,有 17 名患者在手术后立即接受 IORT。我们通过分析接受和未接受 IORT 治疗的胰腺癌手术后患者的腹腔液(PF)和血液中的免疫反应变化,研究 IORT 诱导的免疫反应变化。此外,我们用 PF 处理三种胰腺细胞系,观察增殖和活性变化。

结果

接受 IORT 治疗的患者 PF 中参与 PI3K/SMAD 通路的细胞因子水平升高。此外,IORT 治疗的 PF 抑制了胰腺癌细胞的生长、迁移和侵袭。接受 IORT 治疗的患者血液中淋巴细胞群的变化表明免疫反应增强。

结论

基于血液中免疫细胞的特征和量化以及 PF 中的细胞因子水平,我们得出结论,IORT 通过激活免疫反应产生抗肿瘤作用,从而可能预防胰腺癌复发。

临床试验注册

NCT03273374。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f34f/8507125/3417e9f205c7/12885_2021_8807_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f34f/8507125/ab37ff9154ba/12885_2021_8807_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f34f/8507125/362d58dad578/12885_2021_8807_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f34f/8507125/620eb3790354/12885_2021_8807_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f34f/8507125/7f3d781269be/12885_2021_8807_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f34f/8507125/3417e9f205c7/12885_2021_8807_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f34f/8507125/ab37ff9154ba/12885_2021_8807_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f34f/8507125/362d58dad578/12885_2021_8807_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f34f/8507125/620eb3790354/12885_2021_8807_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f34f/8507125/7f3d781269be/12885_2021_8807_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f34f/8507125/3417e9f205c7/12885_2021_8807_Fig5_HTML.jpg

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