Human blood cell transcriptomics unveils dynamic systemic immune modulation along colorectal cancer progression.
Details
State: Public
Version: Final published version
License: CC BY-NC 4.0
Serval ID
serval:BIB_BF31C73BFB08
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Human blood cell transcriptomics unveils dynamic systemic immune modulation along colorectal cancer progression.
Journal
Journal for immunotherapy of cancer
ISSN
2051-1426 (Electronic)
ISSN-L
2051-1426
Publication state
Published
Issued date
21/11/2024
Peer-reviewed
Oui
Volume
12
Number
11
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Abstract
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. CRC deaths can be reduced with prevention and early diagnosis. Circulating tumor DNA-based liquid biopsies, are emerging tools for cancer detection. However, the tumor-signal-dependent nature of this approach results in low sensitivity in precancerous and early CRC stages. Here we propose the host immune response to the onset of cancer as an alternative approach for early detection of CRC.
We perform whole transcriptome analysis of peripheral blood mononuclear cells (PBMCs) isolated from individuals with CRC, precancerous lesions or negative colonoscopy in two independent cohorts using next-generation sequencing.
We discover and validate novel early CRC RNA biomarkers. Taking into account, and adjusting for, the sensitivity of PBMCs transcriptomes to processing times, we report distinct transcriptomic changes in the periphery related to specific CRC stages. Activation of innate immunity is already detectable in the peripheral blood of individuals with pre-malignant advanced adenomas. This immune response is followed by signs of transient B-cell activation and sustained inhibition of T-cell responses along CRC progression, whereby at late stages, protumoral myeloid cells, wound healing and coagulation processes prevail. Moreover, some biomarkers show similar dysregulation in tumors and are implicated in known pathways of CRC pathophysiology.
The strong systemic immune modulation triggered during CRC progression leads to previously unnoticed alterations detectable in PBMCs, paving the way for the development of an early CRC screening blood test, incorporating 226 validated biomarkers identified through immunotranscriptomics.
We perform whole transcriptome analysis of peripheral blood mononuclear cells (PBMCs) isolated from individuals with CRC, precancerous lesions or negative colonoscopy in two independent cohorts using next-generation sequencing.
We discover and validate novel early CRC RNA biomarkers. Taking into account, and adjusting for, the sensitivity of PBMCs transcriptomes to processing times, we report distinct transcriptomic changes in the periphery related to specific CRC stages. Activation of innate immunity is already detectable in the peripheral blood of individuals with pre-malignant advanced adenomas. This immune response is followed by signs of transient B-cell activation and sustained inhibition of T-cell responses along CRC progression, whereby at late stages, protumoral myeloid cells, wound healing and coagulation processes prevail. Moreover, some biomarkers show similar dysregulation in tumors and are implicated in known pathways of CRC pathophysiology.
The strong systemic immune modulation triggered during CRC progression leads to previously unnoticed alterations detectable in PBMCs, paving the way for the development of an early CRC screening blood test, incorporating 226 validated biomarkers identified through immunotranscriptomics.
Keywords
Humans, Colorectal Neoplasms/genetics, Colorectal Neoplasms/immunology, Transcriptome, Disease Progression, Male, Female, Biomarkers, Tumor/genetics, Middle Aged, Aged, Leukocytes, Mononuclear/metabolism, Leukocytes, Mononuclear/immunology, Gene Expression Profiling/methods, B cell, Biomarker, Colorectal Cancer, Neutrophil, Next generation sequencing - NGS
Pubmed
Web of science
Open Access
Yes
Create date
02/12/2024 13:56
Last modification date
21/01/2025 7:26