FOLFOX和贝伐单抗（FOLFOX-Bev）的联合治疗对于晚期结直肠癌（CRC）是一种有前景的治疗方法。然而，肿瘤微环境对于FOLFOX-Bev的反应仍然较少被探究。我们对来自患者在治疗前后的CRC样本进行了单细胞转录组分析，以了解与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细胞的细胞毒性作用，从而增强了抗肿瘤免疫反应。相反地，FOLFOX-Bev损害了肿瘤相关巨噬细胞、浆细胞和肿瘤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，可能会影响非癌细胞的功能。我们的发现为FOLFOX-Bev治疗对于晚期CRC反应的分子机制提供了有价值的见解，并强调了改善该治疗策略有效性的潜在靶点。版权所有：2023年杨某、杨某、马某、李某、赵某和杨某。

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.Copyright © 2023 Yang, Yang, Ma, Li, Zhao and Yang.