通过免疫调节疗法利用抗肿瘤免疫从根本上改变了原发性肝癌（PLC）的治疗。然而，这给临床前研究带来了重大挑战。迫切需要新的 PLC 免疫学相关模型来改善从实验室到临床的转化，探索和预测有效的组合疗法，帮助新药发现并开发个性化治疗方式。我们使用源自人体精密切割组织切片 (PCTS)切除肿瘤以创建患者特异性免疫功能疾病模型，该模型捕获肿瘤和肿瘤微环境的多方面且复杂的异质性。通过组织学分析、增殖/细胞死亡标记物检测、HPLC 检测 ATP 含量，在 8 天的离体培养过程中纵向评估组织结构、肿瘤活力以及对单药和联合疗法的治疗反应。使用 PCR 和免疫荧光评估免疫细胞浸润。通过Quantigene RNA测定对检查点受体表达进行定量。优化培养条件后，PCTS保持了原始的组织结构，包括肿瘤形态、间质和肿瘤浸润的白细胞。此外，随着时间的推移，PCTS 保留了肿瘤特异性免疫表型，这表明 PCTS 可用于研究免疫治疗药物疗效和识别无反应性。在这里，我们描述了 PCTS 模型的特征，并证明了其作为强大的临床前工具的有效性，将显着支持开发PLC 的成功（免疫）治疗策略。伦敦肝脏研究基金会。版权所有 © 2023 作者。由 Elsevier B.V. 出版。保留所有权利。

The exploitation of anti-tumour immunity, harnessed through immunomodulatory therapies, has fundamentally changed the treatment of primary liver cancer (PLC). However, this has posed significant challenges in preclinical research. Novel immunologically relevant models for PLC are urgently required to improve the translation from bench to bedside and back, explore and predict effective combinatorial therapies, aid novel drug discovery and develop personalised treatment modalities.We used human precision-cut tissue slices (PCTS) derived from resected tumours to create a patient-specific immunocompetent disease model that captures the multifaceted and intricate heterogeneity of the tumour and the tumour microenvironment. Tissue architecture, tumour viability and treatment response to single agent and combination therapies were assessed longitudinally over 8 days of ex vivo culture by histological analysis, detection of proliferation/cell death markers, ATP content via HPLC. Immune cell infiltrate was assessed using PCR and immunofluorescence. Checkpoint receptor expression was quantified via Quantigene RNA assay.After optimising the culture conditions, PCTS maintained the original tissue architecture, including tumour morphology, stroma and tumour-infiltrated leukocytes. Moreover, PCTS retained the tumour-specific immunophenotype over time, suggesting the utility of PCTS to investigate immunotherapeutic drug efficacy and identify non-responsiveness.Here we have characterised the PCTS model and demonstrated its effectiveness as a robust preclinical tool that will significantly support the development of successful (immuno)therapeutic strategies for PLC.Foundation for Liver Research, London.Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.