由于治疗选择有限，复发性或转移性宫颈癌（r/m CC）通常预后不良。缺乏能准确反映宫颈癌（CC）生物学和基因组异质性的临床前模型，制约了新型治疗策略的开发。以此为目标，我们旨在建立一个大型来自患者的异种移植（PDX）生物样本库，评估PDX模型与患者原发肿瘤组织之间生物学指标的一致性，并探索其用于评估患者对传统和新型治疗的反应的效用。将69个新鲜的宫颈癌肿瘤组织直接植入免疫缺陷小鼠中建立PDX模型。通过苏木精-伊红染色、免疫组化和全外显子测序，基于临床病理特征、蛋白生物标志物水平和基因组特征，比较PDX模型与其相应原发肿瘤（PTs）的一致性。此外，将宫颈癌患者的临床信息、原发肿瘤的RNA转录组和免疫表型整合起来，以确定影响异种移植成功的潜在参数。接着，评估PDX模型是否能够反映患者对化疗的反应。最后，利用PDX模型和PDX衍生的器官样本（PDXO），评估奈替尼和采用细胞转移免疫疗法（ACT）联合策略对HER2基因突变的宫颈癌患者的治疗效果。我们建立了一个宫颈癌PDX生物样本库，成功率为63.8%（44/69）。建立的PDX肿瘤的主要特征，包括临床病理特征、蛋白标志物的表达水平（包括Ki67、α-平滑肌肌动蛋白和p16）和基因组特征，与其PTs高度一致。此外，异种移植的成功可能受到原发肿瘤大小、滤泡辅助T细胞的存在和细胞黏附相关基因在原发肿瘤组织中的表达的影响。宫颈癌衍生的PDX模型能够重现患者对化疗的反应。在PDX模型中，一种新的治疗策略，即ACT与奈替尼的联合应用，被证明能有效抑制源自HER2基因突变宫颈癌患者的PDX肿瘤的生长。我们建立了迄今为止最大的宫颈癌PDX生物样本库，成功率较高，能够保留患者活检样本的组织病理学和遗传特征，重现患者对传统治疗的反应，并且能够评估新型宫颈癌治疗方法的疗效。© 2023年BioMed Central有限公司，Springer Nature的一部分。

Recurrent or metastatic cervical cancer (r/m CC) often has poor prognosis owing to its limited treatment options. The development of novel therapeutic strategies has been hindered by the lack of preclinical models that accurately reflect the biological and genomic heterogeneity of cervical cancer (CC). Herein, we aimed to establish a large patient-derived xenograft (PDX) biobank for CC, evaluate the consistency of the biologic indicators between PDX and primary tumor tissues of patients, and explore its utility for assessing patient's response to conventional and novel therapies.Sixty-nine fresh CC tumor tissues were implanted directly into immunodeficient mice to establish PDX models. The concordance of the PDX models with their corresponding primary tumors (PTs) was compared based on the clinical pathological features, protein biomarker levels, and genomic features through hematoxylin & eosin staining, immunohistochemistry, and whole exome sequencing, respectively. Moreover, the clinical information of CC patients, RNA transcriptome and immune phenotyping of primary tumors were integrated to identify the potential parameters that could affect the success of xenograft engraftment. Subsequently, PDX model was evaluated for its capacity to mirror patient's response to chemotherapy. Finally, PDX model and PDX-derived organoid (PDXO) were utilized to evaluate the therapeutic efficacy of neratinib and adoptive cell therapy (ACT) combination strategy for CC patients with human epidermal growth factor receptor 2 (HER2) mutation.We established a PDX biobank for CC with a success rate of 63.8% (44/69). The primary features of established PDX tumors, including clinicopathological features, the expression levels of protein biomarkers including Ki67, α-smooth muscle actin, and p16, and genomics, were highly consistent with their PTs. Furthermore, xenograft engraftment was likely influenced by the primary tumor size, the presence of follicular helper T cells and the expression of cell adhesion-related genes in primary tumor tissue. The CC derived PDX models were capable of recapitulating the patient's response to chemotherapy. In a PDX model, a novel therapeutic strategy, the combination of ACT and neratinib, was shown to effectively inhibit the growth of PDX tumors derived from CC patients with HER2-mutation.We established by far the largest PDX biobank with a high engraftment rate for CC that preserves the histopathological and genetic characteristics of patient's biopsy samples, recapitulates patient's response to conventional therapy, and is capable of evaluating the efficacy of novel therapeutic modalities for CC.© 2023. BioMed Central Ltd., part of Springer Nature.