Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway.
Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway.
Cancer Med. 2023 May;12(10):11589-11601. doi: 10.1002/cam4.5784. Epub 2023 Mar 13.
Immunocompetent murine models are important tools for preclinical evaluation of immunotherapies. Here, six different immunocompetent tumor models based on four different cell lines were characterized, including metastatic lung cancer (CMT 167), triple-negative breast cancer (4T1), pancreatic cancer (KPCY), and colon cancer (MC38). The tumors were implanted subcutaneously or orthotopically before the animals were treated with anti-PD1 checkpoint inhibitor. A range of innate and adaptive immune cells were then quantified by flow cytometry of single-cell suspensions from the tumors. Furthermore, confocal laser scanning microscopy was used to quantify the density and distribution of T-cells in frozen sections. A model-dependent cellular immune landscape was observed, with variable responsiveness toward anti-PD1, ranging from the most responsive MC38 colon cancer model to the least responsive 4T1 breast cancer model. The study provides an overview of the immune landscape of these tumor models, and a foundation for further elucidation of pro-tumor and anti-tumor mechanisms behind heterogeneous responses towards immunotherapies.
免疫功能正常的小鼠模型是免疫疗法临床前评估的重要工具。在这里,我们对基于四种不同细胞系的六种不同的免疫功能正常的肿瘤模型进行了特征描述,包括转移性肺癌(CMT 167)、三阴性乳腺癌(4T1)、胰腺癌(KPCY)和结肠癌(MC38)。在对动物进行抗 PD1 检查点抑制剂治疗之前,将肿瘤皮下或原位植入。然后通过肿瘤单细胞悬液的流式细胞术对多种固有和适应性免疫细胞进行定量。此外,还使用共聚焦激光扫描显微镜对冷冻切片中 T 细胞的密度和分布进行定量。观察到一种依赖于模型的细胞免疫景观,对抗 PD1 的反应性各不相同,从最敏感的 MC38 结肠癌模型到最不敏感的 4T1 乳腺癌模型。该研究概述了这些肿瘤模型的免疫景观,并为进一步阐明免疫疗法异质性反应背后的促肿瘤和抗肿瘤机制奠定了基础。