التفاصيل البيبلوغرافية
| العنوان: |
Cancer‐associated fibroblasts contribute to the immunosuppressive landscape and influence the efficacy of the combination therapy of PD‐1 inhibitors and antiangiogenic agents in hepatocellular carcinoma. |
| المؤلفون: |
Chen, Qiurui, Wang, Xuejia, Zheng, Yichen, Ye, Ting, Liu, Jing, Wang, Jin‐Quan, Zhang, Wen‐feng, Wu, Feng‐Lin, Bo, Huaben, Shao, Hongwei, Zhang, Rongxin, Shen, Han |
| المصدر: |
Cancer (0008543X); Nov2023, Vol. 129 Issue 21, p3405-3416, 12p |
| مصطلحات موضوعية: |
NEOVASCULARIZATION inhibitors, HEPATOCELLULAR carcinoma, PROGRAMMED cell death 1 receptors, RNA sequencing, MTOR inhibitors, CHEMOEMBOLIZATION |
| مستخلص: |
Background: Chronic inflammation is considered the most critical predisposing factor of hepatocellular carcinoma (HCC), with inflammatory cell heterogeneity, hepatic fibrosis accumulation, and abnormal vascular proliferation as prominent features of the HCC tumor microenvironment (TME). Cancer‐associated fibroblasts (CAFs) play a key role in HCC TME remodeling. Therefore, the level of abundance of CAFs may significantly affect the prognosis and outcome in HCC patients. Methods: Unsupervised clustering was performed based on 39 genes related to CAFs in HCC identified by single‐cell RNA sequencing data. Patients of bulk RNA were grouped into CAF low abundance cluster and high abundance clusters. Subsequently, prognosis, immune infiltration landscape, metabolism, and treatment response between the two clusters were investigated and validated by immunohistochemistry. Results: Patients in the CAF high cluster had a higher level of inflammatory cell infiltration, a more significant immunosuppressive microenvironment, and a significantly worse prognosis than those in the low cluster. At the metabolic level, the CAF high cluster had lower levels of aerobic oxidation and higher angiogenic scores. Drug treatment response prediction indicated that the CAF high cluster could have a better response to PD‐1 inhibitors and conventional chemotherapeutic agents for HCC such as anti‐angiogenic drugs, whereas CAF low cluster may be more sensitive to transarterial chemoembolization treatment. Conclusions: This study not only revealed the TME characteristics of HCC with the difference in CAF abundance but also further confirmed that the combination therapy of PD‐1 inhibitors and anti‐angiogenic drugs may be more valuable for patients with high CAF abundance. Cancer‐associated fibroblast (CAF)‐related genes obtained from single‐cell RNA sequencing data analysis were used to cluster four hepatocellular carcinoma bulk RNA cohorts and higher levels of immune infiltration were found in the CAF high cluster with poorer prognosis and high angiogenic activity. Because of greater sensitivity to immunotherapy and anti‐angiogenic drugs, the authors validated the effectiveness of PD‐1 inhibitors combined with anti‐angiogenic drugs in CAF high cluster. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
