Human blood cell transcriptomics unveils dynamic systemic immune modulation along colorectal cancer progression
Background 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 a...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2024-11-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/11/e009888.full |
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| author | Pedro J Romero Mauro Delorenzi Amaia Martínez-Usatorre Laura Ciarloni Noushin Hadadi Eric Durandau Sylvain Monnier-Benoit Paolo Angelino Victoria Wosika Alessandra Jordano Conforte Sara S Fonseca Costa Hector Fabio Satizabal Jérémie Despraz Andres Perez-Uribe Stephan Morgenthaler Brian Hashemi Sahar Hosseinian-Ehrensberger |
| author_facet | Pedro J Romero Mauro Delorenzi Amaia Martínez-Usatorre Laura Ciarloni Noushin Hadadi Eric Durandau Sylvain Monnier-Benoit Paolo Angelino Victoria Wosika Alessandra Jordano Conforte Sara S Fonseca Costa Hector Fabio Satizabal Jérémie Despraz Andres Perez-Uribe Stephan Morgenthaler Brian Hashemi Sahar Hosseinian-Ehrensberger |
| author_sort | Pedro J Romero |
| collection | DOAJ |
| description | Background 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.Methods 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.Results 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.Conclusions 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. |
| format | Article |
| id | doaj-art-b2564c8ab94d400986bcb423de67f0ee |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-b2564c8ab94d400986bcb423de67f0ee2025-01-27T08:05:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-11-01121110.1136/jitc-2024-009888Human blood cell transcriptomics unveils dynamic systemic immune modulation along colorectal cancer progressionPedro J Romero0Mauro Delorenzi1Amaia Martínez-Usatorre2Laura Ciarloni3Noushin Hadadi4Eric Durandau5Sylvain Monnier-Benoit6Paolo Angelino7Victoria Wosika8Alessandra Jordano Conforte9Sara S Fonseca Costa10Hector Fabio Satizabal11Jérémie Despraz12Andres Perez-Uribe13Stephan Morgenthaler14Brian Hashemi15Sahar Hosseinian-Ehrensberger16Novigenix SA, Epalinges, SwitzerlandUniversity of Lausanne, Lausanne, SwitzerlandNovigenix SA, Epalinges, SwitzerlandNovigenix SA, Epalinges, SwitzerlandNovigenix SA, Epalinges, SwitzerlandNovigenix SA, Epalinges, SwitzerlandNovigenix SA, Epalinges, SwitzerlandSwiss Institute of Bioinformatics, Lausanne, SwitzerlandNovigenix SA, Epalinges, SwitzerlandNovigenix SA, Epalinges, SwitzerlandNovigenix SA, Epalinges, SwitzerlandInstitute for Information and Communication Technologies (IICT), School of Engineering and Management Vaud, HES-SO, University of Applied Sciences and Arts Western, Yverdon-les-Bains, SwitzerlandInstitute for Information and Communication Technologies (IICT), School of Engineering and Management Vaud, HES-SO, University of Applied Sciences and Arts Western, Yverdon-les-Bains, SwitzerlandInstitute for Information and Communication Technologies (IICT), School of Engineering and Management Vaud, HES-SO, University of Applied Sciences and Arts Western, Yverdon-les-Bains, SwitzerlandInstitute of Mathematics, EPFL, Lausanne, SwitzerlandNovigenix SA, Epalinges, SwitzerlandNovigenix SA, Epalinges, SwitzerlandBackground 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.Methods 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.Results 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.Conclusions 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.https://jitc.bmj.com/content/12/11/e009888.full |
| spellingShingle | Pedro J Romero Mauro Delorenzi Amaia Martínez-Usatorre Laura Ciarloni Noushin Hadadi Eric Durandau Sylvain Monnier-Benoit Paolo Angelino Victoria Wosika Alessandra Jordano Conforte Sara S Fonseca Costa Hector Fabio Satizabal Jérémie Despraz Andres Perez-Uribe Stephan Morgenthaler Brian Hashemi Sahar Hosseinian-Ehrensberger Human blood cell transcriptomics unveils dynamic systemic immune modulation along colorectal cancer progression Journal for ImmunoTherapy of Cancer |
| title | Human blood cell transcriptomics unveils dynamic systemic immune modulation along colorectal cancer progression |
| title_full | Human blood cell transcriptomics unveils dynamic systemic immune modulation along colorectal cancer progression |
| title_fullStr | Human blood cell transcriptomics unveils dynamic systemic immune modulation along colorectal cancer progression |
| title_full_unstemmed | Human blood cell transcriptomics unveils dynamic systemic immune modulation along colorectal cancer progression |
| title_short | Human blood cell transcriptomics unveils dynamic systemic immune modulation along colorectal cancer progression |
| title_sort | human blood cell transcriptomics unveils dynamic systemic immune modulation along colorectal cancer progression |
| url | https://jitc.bmj.com/content/12/11/e009888.full |
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