Single-cell analysis reveals cellular reprogramming in advanced colon cancer following FOLFOX-bevacizumab treatment

Abstract

IntroductionThe 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.MethodsWe 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.ResultsWe 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.DiscussionOur 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.

Spatial mapping of the hepatocellular carcinoma landscape identifies unique intratumoural perivascular-immune neighbourhoods

“…Immune-vascular cross-talk underpins the rationale for using bevacizumab, an anti-VEGFA monoclonal antibody that normalises tumour vasculature, in conjunction with immune checkpoint inhibitors in advanced unresectable HCC 5 . Advanced colorectal cancer patients receiving combined FOLFOX and bevacizumab have decreased VEGFB-mediated angiogenesis, including reduced myeloid cell-endothelial cell communication via VEGF as identified by single-cell RNA sequencing 59 . In pre-clinical HCC models, anti-angiogenic therapy in conjunction with anti-PD-1 therapy further promotes vascular normalisation mediated by CD4 + T cells 16 .…”

Single‐cell transcriptomics reveals antigen‐presenting capacity and therapeutic resistance potential of immunomodulatory endothelial cells in colorectal cancer

“…Unfortunately, due to ECs only constitute a small fraction of tumor tissues, it is difficult to study specific EC phenotypes. 7,13 Integrating decentralized datasets could be an important way to address this situation. 14 In this study, four CRC scRNA-seq datasets were integrated to distinguish EC subsets within stromal cells and validated using an independent scRNA-seq validation dataset.…”