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

Meiling Yang; Ciqiu Yang; Dong Ma; Zijun Li; Wei Zhao; Dongyang Yang

doi:10.3389/fonc.2023.1219642

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

Front Oncol. 2023 Jul 28:13:1219642. doi: 10.3389/fonc.2023.1219642. eCollection 2023.

Authors

Meiling Yang^{1

2}, Ciqiu Yang³, Dong Ma⁴, Zijun Li⁵, Wei Zhao^{1

2

6}, Dongyang Yang⁴

Affiliations

¹ Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
² Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
³ Department of Breast Cancer, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
⁴ Medical Oncology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
⁵ Guangdong Provincial Institute of Geriatrics, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
⁶ Key Laboratory of Stem Cells and Tissue Engineering (Sun Yat-Sen University), Ministry of Education, Guangzhou, China.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Discussion: 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.

Keywords: FOLFOX; VEGF; advanced colorectal cancer; bevacizumab; single-cell transcriptomic analysis.

Grants and funding

This work was supported by the National Natural Science Foundation of China (81972651, and 82172698), the High‐level Hospital Construction Project (DFJHBF202102) and CSCO-Qilu Oncology Research Project (Y-QL2019-0360).