Shintani Yasushi, Kimura Toru, Funaki Soichiro, Ose Naoko, Kanou Takashi, Fukui Eriko
Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University, 2-2-L5, Yamadaoka, Suita, Osaka 565-0871, Japan.
Cancers (Basel). 2023 Jan 4;15(2):335. doi: 10.3390/cancers15020335.
Lung cancer is the most frequently diagnosed cancer and the leading cause of cancer death worldwide. The most common lung cancer is non-small cell lung cancer (NSCLC), with an overall 5-year survival rate of around 20% because NSCLC is a metastatic disease. A better understanding of the mechanism underlying lung cancer metastasis is therefore urgently needed. The tumor microenvironment involves different types of stromal cells and functions as key components in the progression of NSCLC. Through epithelial-mesenchymal transition (EMT), in which epithelial cells lose their polarity and acquire mesenchymal potential, cancer cells acquire metastatic abilities, as well as cancer stem-cell-like potential. We previously reported that cancer-associated fibroblasts (CAFs) interact with lung cancer cells to allow for the acquisition of malignancy and treatment resistance by paracrine loops via EMT signals in the tumor microenvironment. Furthermore, CAFs regulate the cytotoxic activity of immune cells via various cytokines and chemokines, creating a microenvironment of immune tolerance. Regulation of CAFs can therefore affect immune responses. Recent research has shown several roles of CAFs in NSCLC tumorigenesis, owing to their heterogeneity, so molecular markers of CAFs should be elucidated to better classify tumor-promoting subtypes and facilitate the establishment of CAF-specific targeted therapies. CAF-targeted cancer treatments may suppress EMT and regulate the niche of cancer stem cells and the immunosuppressive network and thus may prove useful for NSCLC treatment through multiple mechanisms.
肺癌是全球最常被诊断出的癌症，也是癌症死亡的主要原因。最常见的肺癌是非小细胞肺癌（NSCLC），由于NSCLC是一种转移性疾病，其总体5年生存率约为20%。因此，迫切需要更好地了解肺癌转移的潜在机制。肿瘤微环境涉及不同类型的基质细胞，是NSCLC进展的关键组成部分。通过上皮-间质转化（EMT），上皮细胞失去极性并获得间质潜能，癌细胞获得转移能力以及癌症干细胞样潜能。我们之前报道过，癌症相关成纤维细胞（CAF）与肺癌细胞相互作用，通过肿瘤微环境中的EMT信号以旁分泌环的方式使癌细胞获得恶性特征和治疗抗性。此外，CAF通过各种细胞因子和趋化因子调节免疫细胞的细胞毒性活性，营造免疫耐受的微环境。因此，对CAF的调控会影响免疫反应。由于CAF的异质性，最近的研究显示了CAF在NSCLC肿瘤发生中的多种作用，因此应阐明CAF的分子标志物，以更好地分类促肿瘤亚型，并促进CAF特异性靶向治疗的建立。针对CAF的癌症治疗可能会抑制EMT，调节癌症干细胞的生态位和免疫抑制网络，从而可能通过多种机制对NSCLC治疗有用。
