Department of Surgery, Houston Methodist Research Institute, Houston, TX, USA.
Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA.
Sci Rep. 2018 Nov 8;8(1):16569. doi: 10.1038/s41598-018-34983-7.
The immune system and tumor microenvironment play a decisive role in tumor progression. We developed a novel model to better understand tumor progression and interaction with immune cells and the cellular components. We grew 393 P non-metastatic and 344SQ metastatic murine cells in an acellular metastatic lung cancer model, where both cell lines formed circulating tumor cells (CTC) and metastatic lesions. When the CTC from this model were placed in the tail vein of nu/nu mice, both cell lines formed metastatic lesions. However, in syngeneic immune-competent mice, the CTC from the non-metastatic cell line did not metastasize while the CTC from the metastatic cell line metastasized. When we placed the activated immune cells in the cellular lung model, it decreased CTC and metastatic lesion formation for the non-metastatic cell line while it had no impact on metastatic cell line. The metastatic cell line had a significant increase in expression of programmed death-ligand 1 (PDL-1) compared to the non-metastatic cell line in the model. Overall, the immune cells showed an impact on viability of CTC for cell lines with a decreased expression of PDL-1 that leads to decreased metastatic lesion formation. Further studies are needed to understand the subtype of immune cells and mechanism of decreased CTC viability and metastasis inhibition.
免疫系统和肿瘤微环境在肿瘤进展中起着决定性的作用。我们开发了一种新的模型，以更好地了解肿瘤的进展以及与免疫细胞和细胞成分的相互作用。我们在非转移性 393P 和转移性 344SQ 鼠细胞的无细胞转移性肺癌模型中进行培养，这两种细胞系均形成循环肿瘤细胞（CTC）和转移性病变。当将该模型中的 CTC 置于无胸腺 nu/nu 小鼠的尾静脉中时，这两种细胞系均形成转移性病变。然而，在同种免疫功能正常的小鼠中，非转移性细胞系的 CTC 未发生转移，而转移性细胞系的 CTC 则发生了转移。当我们将激活的免疫细胞置于细胞性肺模型中时，非转移性细胞系的 CTC 和转移性病变形成减少，而对转移性细胞系没有影响。与非转移性细胞系相比，模型中的转移性细胞系程序性死亡配体 1（PDL-1）的表达显著增加。总的来说，免疫细胞对 PDL-1 表达降低的 CTC 的存活能力产生了影响，导致转移性病变形成减少。需要进一步的研究来了解免疫细胞的亚类以及降低 CTC 存活能力和抑制转移的机制。
