Single-cell transcriptome analysis reveals immunosuppressive landscape in overweight and obese colorectal cancer.
J Transl Med
; 22(1): 134, 2024 02 04.
Article
en En
| MEDLINE
| ID: mdl-38311726
ABSTRACT
BACKGROUND:
Overweight and obesity are established risk factors for various types of cancers including colorectal cancer (CRC). However the underlying molecular mechanisms remain unclear. An in-depth understanding of the oncologic characteristics of overweight and obese CRC at the single-cell level can provide valuable insights for the development of more effective treatment strategies for CRC.METHODS:
We conducted single-cell RNA sequencing (scRNA-seq) analysis on tumor and adjacent normal colorectal samples from 15 overweight/obese and 15 normal-weight CRC patients. Immunological and metabolic differences between overweight/obese CRC and non-obese CRC were characterized.RESULTS:
We obtained single-cell transcriptomics data from a total of 192,785 cells across all samples. By evaluating marker gene expression patterns, we annotated nine main cell types in the CRC ecosystem. Specifically, we found that the cytotoxic function of effector T cells and NK cells was impaired in overweight/obese CRC compared with non-obese CRC, relating to its metabolic dysregulation. CD4+T cells in overweight/obese CRC exhibited higher expression of immune checkpoint molecules. The antigen-presenting ability of DCs and B cells is down-regulated in overweight/obese CRC, which may further aggravate the immunosuppression of overweight/obese CRC. Additionally, dysfunctional stromal cells were identified, potentially promoting invasion and metastasis in overweight/obese CRC. Furthermore, we discovered the up-regulated metabolism of glycolysis and lipids of tumor cells in overweight/obese CRC, which may impact the metabolism and function of immune cells. We also identified inhibitory interactions between tumor cells and T cells in overweight/obese CRC.CONCLUSIONS:
The study demonstrated that overweight/obese CRC has a more immunosuppressive microenvironment and distinct metabolic reprogramming characterized by increased of glycolysis and lipid metabolism. These findings may have implications for the development of novel therapeutic strategies for overweight/obese CRC patients.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales
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Sobrepeso
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
J Transl Med
Año:
2024
Tipo del documento:
Article
País de afiliación:
China