两种可移植的同基因小鼠黑色素瘤模型的功能比较:B16F0和YUMM1.7。

A functional comparison of two transplantable syngeneic mouse models of melanoma: B16F0 and YUMM1.7.

作者信息

Klinke David J, Gould Alanna, Pirkey Anika, Razazan Atefeh, Deng Wentao

机构信息

Department of Chemical and Biomedical Engineering, West Virginia University, Morgantown, WV.

Department of Biochemistry, The Medical College of Wisconsin.

出版信息

bioRxiv. 2025 Jun 10:2025.05.09.652938. doi: 10.1101/2025.05.09.652938.

Abstract

The B16 murine melanoma cell lines are considered the gold standard for testing melanoma immunotherapies due to low treatment success rates. However, the clinical relevance of these models has been questioned due to a mutational landscape void of driver mutations typically seen in human melanomas and a tendency to form necrotic cores at high tumor volumes. Creating the YUMM1.7 line addressed these limitations by providing an additional contextually consistent model with a more clinically relevant genetic background. The combined use of both models can generate stronger studies in melanoma immunology and immunotherapy. However, to date, there have been no direct functional comparisons of the characteristics of these two models to inform the design of such studies. To address this, we conducted a series of functional experiments to characterize the kinetics of tumor growth, chemotherapeutic sensitivity, and immunogenicity of these models. We found that the B16F0 model had faster intrinsic tumor growth rates, was more susceptible to lysis by tumor-specific CD8+ T cells, and secreted higher levels of the angiogenic factors VEGF and Ang2. Meanwhile, the YUMM1.7 model was more sensitive to chemotherapeutic treatment, secreted higher levels of chemokines CCL2, CXCL1, and CX3CL1, and showed higher infiltration of lymphocyte and myeloid subsets at the same tumor size. Overall, YUMM1.7 model may be better suited for studies of mechanisms that require a wider observation window and intervention than the B16F0 model, such as immune response. However, angiogenesis and immunotherapy studies may benefit from a more in-depth comparative analyses of both models.

摘要

由于治疗成功率较低,B16小鼠黑色素瘤细胞系被认为是测试黑色素瘤免疫疗法的金标准。然而,由于这些模型的突变图谱缺乏人类黑色素瘤中常见的驱动突变,并且在高肿瘤体积时倾向于形成坏死核心,其临床相关性受到了质疑。创建YUMM1.7细胞系通过提供一个具有更临床相关遗传背景的额外上下文一致模型解决了这些局限性。这两种模型的联合使用可以在黑色素瘤免疫学和免疫治疗方面产生更强有力的研究。然而,迄今为止,尚未对这两种模型的特征进行直接功能比较以指导此类研究的设计。为了解决这个问题,我们进行了一系列功能实验来表征这些模型的肿瘤生长动力学、化疗敏感性和免疫原性。我们发现,B16F0模型具有更快的内在肿瘤生长速率,更容易被肿瘤特异性CD8+T细胞裂解,并且分泌更高水平的血管生成因子VEGF和Ang2。同时,YUMM1.7模型对化疗治疗更敏感,分泌更高水平的趋化因子CCL2、CXCL1和CX3CL1,并且在相同肿瘤大小下显示出更高的淋巴细胞和髓系亚群浸润。总体而言,YUMM1.7模型可能比B16F0模型更适合用于需要比其更宽观察窗口和干预的机制研究,例如免疫反应。然而,血管生成和免疫治疗研究可能受益于对这两种模型进行更深入的比较分析。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba59/12258877/d556b1f0849d/nihpp-2025.05.09.652938v2-f0001.jpg

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