Dataset Information

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

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.

SUBMITTER: Yang M

PROVIDER: S-EPMC10421721 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

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

Yang Meiling M Yang Ciqiu C Ma Dong D Li Zijun Z Zhao Wei W Yang Dongyang D

Frontiers in oncology 20230728

<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>We found that cancer cells with high prol ...[more]

PMID: 37576892

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Project description:PurposeThe tumor microenvironment (TME) consists of a heterogenous cellular milieu that can influence cancer cell behavior. Its characteristics have an impact on treatments such as immunotherapy. These features can be revealed with single-cell RNA sequencing (scRNA-seq). We hypothesized that scRNA-seq analysis of gastric cancer together with paired normal tissue and peripheral blood mononuclear cells (PBMC) would identify critical elements of cellular deregulation not apparent with other approaches.Experimental designscRNA-seq was conducted on seven patients with gastric cancer and one patient with intestinal metaplasia. We sequenced 56,167 cells comprising gastric cancer (32,407 cells), paired normal tissue (18,657 cells), and PBMCs (5,103 cells). Protein expression was validated by multiplex immunofluorescence.ResultsTumor epithelium had copy number alterations, a distinct gene expression program from normal, with intratumor heterogeneity. Gastric cancer TME was significantly enriched for stromal cells, macrophages, dendritic cells (DC), and Tregs. TME-exclusive stromal cells expressed distinct extracellular matrix components than normal. Macrophages were transcriptionally heterogenous and did not conform to a binary M1/M2 paradigm. Tumor DCs had a unique gene expression program compared to PBMC DCs. TME-specific cytotoxic T cells were exhausted with two heterogenous subsets. Helper, cytotoxic T, Treg, and NK cells expressed multiple immune checkpoint or co-stimulatory molecules. Receptor-ligand analysis revealed TME-exclusive intercellular communication.ConclusionsSingle-cell gene expression studies revealed widespread reprogramming across multiple cellular elements in the gastric cancer TME. Cellular remodeling was delineated by changes in cell numbers, transcriptional states, and intercellular interactions. This characterization facilitates understanding of tumor biology and enables identification of novel targets including for immunotherapy.

Project description:BackgroundThe Avastin Registry: Investigation of Effectiveness and Safety (ARIES) study is a prospective, community-based observational cohort study that evaluated the effectiveness and safety of first-line treatment patterns, assessing the impact of chemotherapy choice and treatment duration.MethodsThe ARIES study enrolled patients with metastatic colorectal cancer (mCRC) receiving first-line chemotherapy with bevacizumab and followed them longitudinally. The protocol did not specify treatment regimens or assessments. Analyses included all patients who initiated bevacizumab in combination with either first-line oxaliplatin with infusional 5-fluorouracil and leucovorin (FOLFOX) or irinotecan with infusional 5-fluorouracil and leucovorin (FOLFIRI). Progression-free survival (PFS) and overall survival (OS) times were estimated using Kaplan-Meier methods. Hazard ratios (HRs) were estimated with multivariate Cox regression analysis, adjusting for potential confounding factors.ResultsIn total, 1,550 patients with first-line mCRC were enrolled (median follow-up, 21 months) and most received FOLFOX-bevacizumab (n = 968) or FOLFIRI-bevacizumab (n = 243) as first-line therapy. The baseline characteristics and median treatment duration were generally similar between subgroups. There were no significant differences in the median PFS (10.3 months vs. 10.2 months) or OS (23.7 months vs. 25.5 months) time between the FOLFOX-bevacizumab and FOLFIRI-bevacizumab subgroups, respectively, by unadjusted analyses. Multivariate analyses showed FOLFIRI-bevacizumab resulted in a similar PFS (HR, 1.03; 95% confidence interval [CI], 0.88-1.21) and OS (HR, 0.95; 95% CI, 0.78-1.16) outcome as with FOLFOX-bevacizumab. The incidence proportions of bevacizumab-associated adverse events were similar for FOLFOX- and FOLFIRI-based therapies.ConclusionsIn first-line mCRC patients, the FOLFOX-bevacizumab and FOLFIRI-bevacizumab regimens were associated with similar treatment patterns and clinical outcomes.

Dataset Information

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

Introduction

Methods

Results

Discussion

Publications

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

Similar Datasets

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