Differences in the peripheral blood immune landscape between early-onset and late-onset colorectal cancer

Colorectal cancer (CRC) is a leading cause of cancer-related mortality. While screening has reduced incidence in older adults, cases of early-onset CRC (EOCRC), diagnosed before age 50, are rising, highlighting the need to understand its unique biology. Immune responses, particularly T-cell infiltra...

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Autores: Sánchez-Menéndez, Clara, Rodríguez-Pérez, Jaime, Fuertes, Daniel, Leguizamon, Valentina, González-Sanmartín, María, Mateos, Elena, Cervero Jiménez, Miguel|||0000-0001-9387-7917, San José, Esther, Sanz, Gonzalo, Álvaro, Edurne, Ballestero-Pérez, Araceli, Marti-Gallostra, Marc|||0000-0002-0783-6359, Rueda, José Antonio, Hurtado-Caballero, Elena, Pastor, Carlos, Balaguer, Francesc|||0000-0002-0206-0539, Spinelli, Antonino, Martínez-Laso, Jorge, Torres Tarrés, Montserrat, Perea, José, Coiras, Mayte
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:326469
Acceso en línea:https://ddd.uab.cat/record/326469
https://dx.doi.org/urn:doi:10.3389/fimmu.2025.1692382
Access Level:acceso abierto
Palabra clave:Colorectal neoplasms
Early diagnosis
Immune response
T-cell subsets
Cytokine profiling
Immune biomarkers
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spelling Differences in the peripheral blood immune landscape between early-onset and late-onset colorectal cancerSánchez-Menéndez, ClaraRodríguez-Pérez, JaimeFuertes, DanielLeguizamon, ValentinaGonzález-Sanmartín, MaríaMateos, ElenaCervero Jiménez, Miguel|||0000-0001-9387-7917San José, EstherSanz, GonzaloÁlvaro, EdurneBallestero-Pérez, AraceliMarti-Gallostra, Marc|||0000-0002-0783-6359Rueda, José AntonioHurtado-Caballero, ElenaPastor, CarlosBalaguer, Francesc|||0000-0002-0206-0539Spinelli, AntoninoMartínez-Laso, JorgeTorres Tarrés, MontserratPerea, JoséCoiras, MayteColorectal neoplasmsEarly diagnosisImmune responseT-cell subsetsCytokine profilingImmune biomarkersColorectal cancer (CRC) is a leading cause of cancer-related mortality. While screening has reduced incidence in older adults, cases of early-onset CRC (EOCRC), diagnosed before age 50, are rising, highlighting the need to understand its unique biology. Immune responses, particularly T-cell infiltration measured by the tumor-based Immunoscore, are known predictors of CRC prognosis, but less is known about systemic immune differences by age at diagnosis. Peripheral blood mononuclear cells (PBMCs) from EOCRC (n=19) and late-onset CRC (LOCRC; n=19) participants recruited in Madrid (Spain) were analyzed for immune cell phenotypes, exhaustion markers, soluble cytokines, and metabolic activity. Our study revealed distinct peripheral blood immune profiles differentiating EOCRC from LOCRC. EOCRC patients exhibited a heightened proinflammatory environment, with increased functional capacity of CD4+ Th1, Th9, and Th17 subsets to produce IFNg, IL-9, and IL-17A, respectively, and increased plasma levels of IFNg and CXCL8/IL-8. This suggests an active but potentially ineffective immune response. Conversely, LOCRC patients showed hallmarks of immunosenescence and chronic inflammation, including impaired cytokine production, higher frequencies of CD8+ Tgd and Th22 cells, and increased plasma CCL13/MCP-4, consistent with tissue remodeling and immune suppression. Biomarkers distinguishing EOCRC included reduced Th22 and CD8+ Tgd cell frequencies and higher NKT-like cells with increased IL-13 production by Th22 cells. EOCRC and LOCRC involved different immune mechanisms, where EOCRC showed an altered proinflammatory environment with preserved regulatory pathways, while LOCRC reflected age-related immune decline and inflammaging. Peripheral blood immune profiling offers a minimally invasive liquid Immunoscore for early detection and enables personalized immunotherapies for age-related immune landscapes, particularly benefiting younger individuals at risk of EOCRC. 22025-01-0120252025-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/326469https://dx.doi.org/urn:doi:10.3389/fimmu.2025.1692382reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI20/0974Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI24/0729Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2022-141317OB-I00open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3264692026-06-06T12:50:31Z
dc.title.none.fl_str_mv Differences in the peripheral blood immune landscape between early-onset and late-onset colorectal cancer
title Differences in the peripheral blood immune landscape between early-onset and late-onset colorectal cancer
spellingShingle Differences in the peripheral blood immune landscape between early-onset and late-onset colorectal cancer
Sánchez-Menéndez, Clara
Colorectal neoplasms
Early diagnosis
Immune response
T-cell subsets
Cytokine profiling
Immune biomarkers
title_short Differences in the peripheral blood immune landscape between early-onset and late-onset colorectal cancer
title_full Differences in the peripheral blood immune landscape between early-onset and late-onset colorectal cancer
title_fullStr Differences in the peripheral blood immune landscape between early-onset and late-onset colorectal cancer
title_full_unstemmed Differences in the peripheral blood immune landscape between early-onset and late-onset colorectal cancer
title_sort Differences in the peripheral blood immune landscape between early-onset and late-onset colorectal cancer
dc.creator.none.fl_str_mv Sánchez-Menéndez, Clara
Rodríguez-Pérez, Jaime
Fuertes, Daniel
Leguizamon, Valentina
González-Sanmartín, María
Mateos, Elena
Cervero Jiménez, Miguel|||0000-0001-9387-7917
San José, Esther
Sanz, Gonzalo
Álvaro, Edurne
Ballestero-Pérez, Araceli
Marti-Gallostra, Marc|||0000-0002-0783-6359
Rueda, José Antonio
Hurtado-Caballero, Elena
Pastor, Carlos
Balaguer, Francesc|||0000-0002-0206-0539
Spinelli, Antonino
Martínez-Laso, Jorge
Torres Tarrés, Montserrat
Perea, José
Coiras, Mayte
author Sánchez-Menéndez, Clara
author_facet Sánchez-Menéndez, Clara
Rodríguez-Pérez, Jaime
Fuertes, Daniel
Leguizamon, Valentina
González-Sanmartín, María
Mateos, Elena
Cervero Jiménez, Miguel|||0000-0001-9387-7917
San José, Esther
Sanz, Gonzalo
Álvaro, Edurne
Ballestero-Pérez, Araceli
Marti-Gallostra, Marc|||0000-0002-0783-6359
Rueda, José Antonio
Hurtado-Caballero, Elena
Pastor, Carlos
Balaguer, Francesc|||0000-0002-0206-0539
Spinelli, Antonino
Martínez-Laso, Jorge
Torres Tarrés, Montserrat
Perea, José
Coiras, Mayte
author_role author
author2 Rodríguez-Pérez, Jaime
Fuertes, Daniel
Leguizamon, Valentina
González-Sanmartín, María
Mateos, Elena
Cervero Jiménez, Miguel|||0000-0001-9387-7917
San José, Esther
Sanz, Gonzalo
Álvaro, Edurne
Ballestero-Pérez, Araceli
Marti-Gallostra, Marc|||0000-0002-0783-6359
Rueda, José Antonio
Hurtado-Caballero, Elena
Pastor, Carlos
Balaguer, Francesc|||0000-0002-0206-0539
Spinelli, Antonino
Martínez-Laso, Jorge
Torres Tarrés, Montserrat
Perea, José
Coiras, Mayte
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Colorectal neoplasms
Early diagnosis
Immune response
T-cell subsets
Cytokine profiling
Immune biomarkers
topic Colorectal neoplasms
Early diagnosis
Immune response
T-cell subsets
Cytokine profiling
Immune biomarkers
description Colorectal cancer (CRC) is a leading cause of cancer-related mortality. While screening has reduced incidence in older adults, cases of early-onset CRC (EOCRC), diagnosed before age 50, are rising, highlighting the need to understand its unique biology. Immune responses, particularly T-cell infiltration measured by the tumor-based Immunoscore, are known predictors of CRC prognosis, but less is known about systemic immune differences by age at diagnosis. Peripheral blood mononuclear cells (PBMCs) from EOCRC (n=19) and late-onset CRC (LOCRC; n=19) participants recruited in Madrid (Spain) were analyzed for immune cell phenotypes, exhaustion markers, soluble cytokines, and metabolic activity. Our study revealed distinct peripheral blood immune profiles differentiating EOCRC from LOCRC. EOCRC patients exhibited a heightened proinflammatory environment, with increased functional capacity of CD4+ Th1, Th9, and Th17 subsets to produce IFNg, IL-9, and IL-17A, respectively, and increased plasma levels of IFNg and CXCL8/IL-8. This suggests an active but potentially ineffective immune response. Conversely, LOCRC patients showed hallmarks of immunosenescence and chronic inflammation, including impaired cytokine production, higher frequencies of CD8+ Tgd and Th22 cells, and increased plasma CCL13/MCP-4, consistent with tissue remodeling and immune suppression. Biomarkers distinguishing EOCRC included reduced Th22 and CD8+ Tgd cell frequencies and higher NKT-like cells with increased IL-13 production by Th22 cells. EOCRC and LOCRC involved different immune mechanisms, where EOCRC showed an altered proinflammatory environment with preserved regulatory pathways, while LOCRC reflected age-related immune decline and inflammaging. Peripheral blood immune profiling offers a minimally invasive liquid Immunoscore for early detection and enables personalized immunotherapies for age-related immune landscapes, particularly benefiting younger individuals at risk of EOCRC.
publishDate 2025
dc.date.none.fl_str_mv 2
2025-01-01
2025
2025-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/326469
https://dx.doi.org/urn:doi:10.3389/fimmu.2025.1692382
url https://ddd.uab.cat/record/326469
https://dx.doi.org/urn:doi:10.3389/fimmu.2025.1692382
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI20/0974
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI24/0729
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2022-141317OB-I00
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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