Department of Mammary Gland, Dalian Women and Children's Medical Center(Group), No. 1 Dunhuang Road, Dalian 116000, Liaoning Province, China; Department of General Surgery, Shengjing Hospital of China Medical University, No.36.Sanhao Street, Shenyang 110004, Liaoning Province, China.
Department of General Surgery, Shengjing Hospital of China Medical University, No.36.Sanhao Street, Shenyang 110004, Liaoning Province, China.
Biochim Biophys Acta Rev Cancer. 2023 Sep;1878(5):188945. doi: 10.1016/j.bbcan.2023.188945. Epub 2023 Jun 24.
Activated fibroblasts, namely cancer-associated fibroblasts (CAFs), are highly heterogeneous in phenotypes, functions, and origins. CAFs originated from varieties of cell types, including local resident fibroblasts, epithelial cells, mesenchymal stromal cells, or others. These cells participate in tumor angiogenesis, mechanics, drug access, and immune suppression, with the latter being particularly important. It was difficult to distinguish CAFs by subsets due to their complex origins until the use of scRNA-seq. Reprogramming CAFs with TGFβ-RI inhibitor, a CXCR4 blocker, or other methods increases T cells activation and infiltration, together with a decrease in CAFs recruitment, thus improving the prognosis. As depletion of CAFs can't bring clinical benefit, the combination of reprogramming CAFs and immune checkpoint inhibitors (ICIs) come into consideration. It has shown better outcomes compared with monotherapy respectively in basic/preclinical researches, and needs more data on clinical trials. Combination therapy may be a promising and expecting method for treatment of cancer.
活化的成纤维细胞，即癌相关成纤维细胞（CAFs），在表型、功能和起源上具有高度异质性。CAFs 来源于多种细胞类型，包括局部常驻成纤维细胞、上皮细胞、间充质基质细胞或其他细胞。这些细胞参与肿瘤血管生成、力学、药物摄取和免疫抑制，后者尤为重要。由于其起源复杂，直到使用 scRNA-seq 技术，才能够通过亚群来区分 CAFs。使用 TGFβ-RI 抑制剂、CXCR4 阻滞剂或其他方法对 CAFs 进行重编程，可增加 T 细胞的激活和浸润，同时减少 CAFs 的募集，从而改善预后。由于耗尽 CAFs 并不能带来临床获益，因此考虑将 CAFs 重编程与免疫检查点抑制剂（ICI）联合使用。在基础/临床前研究中，与单药治疗相比，联合治疗分别显示出更好的结果，并且需要更多的临床试验数据。联合治疗可能是癌症治疗的一种有前途和令人期待的方法。
