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

Introduction: 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...

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Autores: Sánchez-Menéndez, Clara, Rodríguez-Pérez, Jaime, Fuertes, Daniel, Leguizamon, Valentina, González-Sanmartín, María, Mateos, Elena, Cervero, Miguel, San José, Esther, Sanz, Gonzalo, Álvaro, Edurne, Ballestero-Pérez, Araceli, Martí-Gallostra, Marc, Rueda, José Antonio, Hurtado-Caballero, Elena, Pastor, Carlos, Balaguer, Francesc, Spinelli, Antonino, Martinez-Laso, Jorge, Torres, Montserrat, Perea, José, Coiras, Mayte, Spanish EOCRC Consortium (SECOC)
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/27056
Acceso en línea:https://hdl.handle.net/20.500.12105/27056
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, MiguelSan José, EstherSanz, GonzaloÁlvaro, EdurneBallestero-Pérez, AraceliMartí-Gallostra, MarcRueda, José AntonioHurtado-Caballero, ElenaPastor, CarlosBalaguer, FrancescSpinelli, AntoninoMartinez-Laso, JorgeTorres, MontserratPerea, JoséCoiras, MayteSpanish EOCRC Consortium (SECOC)Colorectal neoplasmsEarly diagnosisImmune responseT-cell subsetsCytokine profilingImmune biomarkersIntroduction: 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. Methods: 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. Results: 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. Conclusions: 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.Frontiers MediaInstituto de Salud Carlos IIIUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Ministerio de Ciencia e Innovación (España)Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)Unión Europea. Comisión Europea. NextGenerationEUComunidad de Madrid (España)20252025-12-1620252025-12-0420252025-12-04research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/ziphttps://hdl.handle.net/20.500.12105/27056reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengNot available Not available Not availableNot available Not available Not availableAgencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PID2022-141317OB-I00 ESTUDIO DEL EFECTO DE LA INMUNOTERAPIA Y DEL TRATAMIENTO ANTIRRETROVIRAL A LARGO PLAZO EN LA EVOLUCION DEL RESERVORIO DEL VIH HACIA UNA CURA FUNCIONALNot available Not available Not availableopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/270562026-06-12T12:43:37Z
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, Miguel
San José, Esther
Sanz, Gonzalo
Álvaro, Edurne
Ballestero-Pérez, Araceli
Martí-Gallostra, Marc
Rueda, José Antonio
Hurtado-Caballero, Elena
Pastor, Carlos
Balaguer, Francesc
Spinelli, Antonino
Martinez-Laso, Jorge
Torres, Montserrat
Perea, José
Coiras, Mayte
Spanish EOCRC Consortium (SECOC)
author Sánchez-Menéndez, Clara
author_facet Sánchez-Menéndez, Clara
Rodríguez-Pérez, Jaime
Fuertes, Daniel
Leguizamon, Valentina
González-Sanmartín, María
Mateos, Elena
Cervero, Miguel
San José, Esther
Sanz, Gonzalo
Álvaro, Edurne
Ballestero-Pérez, Araceli
Martí-Gallostra, Marc
Rueda, José Antonio
Hurtado-Caballero, Elena
Pastor, Carlos
Balaguer, Francesc
Spinelli, Antonino
Martinez-Laso, Jorge
Torres, Montserrat
Perea, José
Coiras, Mayte
Spanish EOCRC Consortium (SECOC)
author_role author
author2 Rodríguez-Pérez, Jaime
Fuertes, Daniel
Leguizamon, Valentina
González-Sanmartín, María
Mateos, Elena
Cervero, Miguel
San José, Esther
Sanz, Gonzalo
Álvaro, Edurne
Ballestero-Pérez, Araceli
Martí-Gallostra, Marc
Rueda, José Antonio
Hurtado-Caballero, Elena
Pastor, Carlos
Balaguer, Francesc
Spinelli, Antonino
Martinez-Laso, Jorge
Torres, Montserrat
Perea, José
Coiras, Mayte
Spanish EOCRC Consortium (SECOC)
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Ministerio de Ciencia e Innovación (España)
Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)
Unión Europea. Comisión Europea. NextGenerationEU
Comunidad de Madrid (España)
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 Introduction: 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. Methods: 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. Results: 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. Conclusions: 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 2025
2025-12-16
2025
2025-12-04
2025
2025-12-04
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
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://hdl.handle.net/20.500.12105/27056
url https://hdl.handle.net/20.500.12105/27056
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Not available Not available Not available
Not available Not available Not available
Agencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PID2022-141317OB-I00 ESTUDIO DEL EFECTO DE LA INMUNOTERAPIA Y DEL TRATAMIENTO ANTIRRETROVIRAL A LARGO PLAZO EN LA EVOLUCION DEL RESERVORIO DEL VIH HACIA UNA CURA FUNCIONAL
Not available Not available Not available
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://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
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/zip
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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