Yang Meiling, Yang Ciqiu, Ma Dong, Li Zijun, Zhao Wei, Yang Dongyang
Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
Front Oncol. 2023 Jul 28;13:1219642. doi: 10.3389/fonc.2023.1219642. eCollection 2023.
The combination of FOLFOX and bevacizumab (FOLFOX-Bev) is a promising treatment for advanced colorectal cancer (CRC). However, the response of the tumor microenvironment to FOLFOX-Bev is still largely unexplored.
We conducted single-cell transcriptomic analysis of CRC samples derived from a patient before and after treatment to gain insights into the cellular changes associated with FOLFOX-Bev treatment.
We found that cancer cells with high proliferative, metastatic, and pro-angiogenic properties respond better to FOLFOX-Bev treatment. Moreover, FOLFOX-Bev enhances CD8 T cell cytotoxicity, thereby boosting the anti-tumor immune response. Conversely, FOLFOX-Bev impairs the functionality of tumor-associated macrophages, plasma cells, and cancer-associated fibroblasts, leading to a decrease in VEGFB-mediated angiogenesis. Furthermore, FOLFOX-Bev treatment reset intercellular communication, which could potentially affect the function of non-cancer cells.
Our findings provide valuable insights into the molecular mechanisms underlying the response of advanced CRC to FOLFOX-Bev treatment and highlight potential targets for improving the efficacy of this treatment strategy.
FOLFOX与贝伐单抗联合使用（FOLFOX-Bev）是晚期结直肠癌（CRC）一种很有前景的治疗方法。然而，肿瘤微环境对FOLFOX-Bev的反应仍很大程度上未被探索。
我们对一名患者治疗前后的CRC样本进行了单细胞转录组分析，以深入了解与FOLFOX-Bev治疗相关的细胞变化。
我们发现具有高增殖、转移和促血管生成特性的癌细胞对FOLFOX-Bev治疗反应更好。此外，FOLFOX-Bev增强了CD8 T细胞的细胞毒性，从而增强了抗肿瘤免疫反应。相反，FOLFOX-Bev损害了肿瘤相关巨噬细胞、浆细胞和癌症相关成纤维细胞的功能，导致VEGFB介导的血管生成减少。此外，FOLFOX-Bev治疗重置了细胞间通讯，这可能会影响非癌细胞的功能。
我们的研究结果为晚期CRC对FOLFOX-Bev治疗反应的分子机制提供了有价值的见解，并突出了改善这种治疗策略疗效的潜在靶点。
