Galectin-1 fosters an immunosuppressive microenvironment in colorectal cancer by reprogramming CD8⁺ regulatory T cells
- Autores
- Cagnoni, Alejandro J.; Giribaldi, María Laura; Blidner, Ada G.; Cutine, Anabela M.; Gatto, Sabrina G.; Morales, Rosa M.; Salatino, Mariana; Abba, Martín Carlos; Croci, Diego O.; Mariño, Karina V.; Rabinovich, Gabriel A.
- Año de publicación
- 2021
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Colorectal cancer (CRC) represents the third most common malignancy and the second leading cause of cancer-related deaths worldwide. Although immunotherapy has taken center stage in mainstream oncology, it has shown limited clinical efficacy in CRC, generating an urgent need for discovery of new biomarkers and potential therapeutic targets. Galectin-1 (Gal-1), an endogenous glycan-binding protein, induces tolerogenic programs and contributes to tumor cell evasion of immune responses. Here, we investigated the relevance of Gal-1 in CRC and explored its modulatory activity within the CD8⁺ regulatory T cell (Treg) compartment. Mice lacking Gal-1 (Lgals1 -/- ) developed a lower number of tumors and showed a decreased frequency of a particular population of CD8⁺CD122⁺PD-1⁺ Tregs in the azoxymethane-dextran sodium sulfate model of colitis-associated CRC. Moreover, silencing of tumor-derived Gal-1 in the syngeneic CT26 CRC model resulted in reduced number and attenuated immunosuppressive capacity of CD8⁺CD122⁺PD-1⁺ Tregs, leading to slower tumor growth. Moreover, stromal Gal-1 also influenced the fitness of CD8⁺ Tregs, highlighting the contribution of both tumor and stromal-derived Gal-1 to this immunoregulatory effect. Finally, bioinformatic analysis of a colorectal adenocarcinoma from The Cancer Genome Atlas dataset revealed a particular signature characterized by high CD8⁺ Treg score and elevated Gal-1 expression, which delineates poor prognosis in human CRC. Our findings identify CD8⁺CD122⁺PD-1⁺ Tregs as a target of the immunoregulatory activity of Gal-1, suggesting a potential immunotherapeutic strategy for the treatment of CRC.
Centro de Investigaciones Inmunológicas Básicas y Aplicadas - Materia
-
Ciencias Médicas
Biología
colorectal cancer
immune escape
Galectin-1
CD8⁺ regulatory T cells - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- http://creativecommons.org/licenses/by-nc-nd/4.0/
- Repositorio
.jpg)
- Institución
- Universidad Nacional de La Plata
- OAI Identificador
- oai:sedici.unlp.edu.ar:10915/146467
Ver los metadatos del registro completo
| id |
SEDICI_9c7d1648a9011d14439a77b4ba4ad5b2 |
|---|---|
| oai_identifier_str |
oai:sedici.unlp.edu.ar:10915/146467 |
| network_acronym_str |
SEDICI |
| repository_id_str |
1329 |
| network_name_str |
SEDICI (UNLP) |
| spelling |
Galectin-1 fosters an immunosuppressive microenvironment in colorectal cancer by reprogramming CD8⁺ regulatory T cellsCagnoni, Alejandro J.Giribaldi, María LauraBlidner, Ada G.Cutine, Anabela M.Gatto, Sabrina G.Morales, Rosa M.Salatino, MarianaAbba, Martín CarlosCroci, Diego O.Mariño, Karina V.Rabinovich, Gabriel A.Ciencias MédicasBiologíacolorectal cancerimmune escapeGalectin-1CD8⁺ regulatory T cellsColorectal cancer (CRC) represents the third most common malignancy and the second leading cause of cancer-related deaths worldwide. Although immunotherapy has taken center stage in mainstream oncology, it has shown limited clinical efficacy in CRC, generating an urgent need for discovery of new biomarkers and potential therapeutic targets. Galectin-1 (Gal-1), an endogenous glycan-binding protein, induces tolerogenic programs and contributes to tumor cell evasion of immune responses. Here, we investigated the relevance of Gal-1 in CRC and explored its modulatory activity within the CD8⁺ regulatory T cell (Treg) compartment. Mice lacking Gal-1 (Lgals1 -/- ) developed a lower number of tumors and showed a decreased frequency of a particular population of CD8⁺CD122⁺PD-1⁺ Tregs in the azoxymethane-dextran sodium sulfate model of colitis-associated CRC. Moreover, silencing of tumor-derived Gal-1 in the syngeneic CT26 CRC model resulted in reduced number and attenuated immunosuppressive capacity of CD8⁺CD122⁺PD-1⁺ Tregs, leading to slower tumor growth. Moreover, stromal Gal-1 also influenced the fitness of CD8⁺ Tregs, highlighting the contribution of both tumor and stromal-derived Gal-1 to this immunoregulatory effect. Finally, bioinformatic analysis of a colorectal adenocarcinoma from The Cancer Genome Atlas dataset revealed a particular signature characterized by high CD8⁺ Treg score and elevated Gal-1 expression, which delineates poor prognosis in human CRC. Our findings identify CD8⁺CD122⁺PD-1⁺ Tregs as a target of the immunoregulatory activity of Gal-1, suggesting a potential immunotherapeutic strategy for the treatment of CRC.Centro de Investigaciones Inmunológicas Básicas y Aplicadas2021-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://sedici.unlp.edu.ar/handle/10915/146467enginfo:eu-repo/semantics/altIdentifier/issn/1091-6490info:eu-repo/semantics/altIdentifier/issn/0027-8424info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.2102950118info:eu-repo/semantics/altIdentifier/pmid/34006646info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-nd/4.0/Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-10-22T17:13:16Zoai:sedici.unlp.edu.ar:10915/146467Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-10-22 17:13:17.177SEDICI (UNLP) - Universidad Nacional de La Platafalse |
| dc.title.none.fl_str_mv |
Galectin-1 fosters an immunosuppressive microenvironment in colorectal cancer by reprogramming CD8⁺ regulatory T cells |
| title |
Galectin-1 fosters an immunosuppressive microenvironment in colorectal cancer by reprogramming CD8⁺ regulatory T cells |
| spellingShingle |
Galectin-1 fosters an immunosuppressive microenvironment in colorectal cancer by reprogramming CD8⁺ regulatory T cells Cagnoni, Alejandro J. Ciencias Médicas Biología colorectal cancer immune escape Galectin-1 CD8⁺ regulatory T cells |
| title_short |
Galectin-1 fosters an immunosuppressive microenvironment in colorectal cancer by reprogramming CD8⁺ regulatory T cells |
| title_full |
Galectin-1 fosters an immunosuppressive microenvironment in colorectal cancer by reprogramming CD8⁺ regulatory T cells |
| title_fullStr |
Galectin-1 fosters an immunosuppressive microenvironment in colorectal cancer by reprogramming CD8⁺ regulatory T cells |
| title_full_unstemmed |
Galectin-1 fosters an immunosuppressive microenvironment in colorectal cancer by reprogramming CD8⁺ regulatory T cells |
| title_sort |
Galectin-1 fosters an immunosuppressive microenvironment in colorectal cancer by reprogramming CD8⁺ regulatory T cells |
| dc.creator.none.fl_str_mv |
Cagnoni, Alejandro J. Giribaldi, María Laura Blidner, Ada G. Cutine, Anabela M. Gatto, Sabrina G. Morales, Rosa M. Salatino, Mariana Abba, Martín Carlos Croci, Diego O. Mariño, Karina V. Rabinovich, Gabriel A. |
| author |
Cagnoni, Alejandro J. |
| author_facet |
Cagnoni, Alejandro J. Giribaldi, María Laura Blidner, Ada G. Cutine, Anabela M. Gatto, Sabrina G. Morales, Rosa M. Salatino, Mariana Abba, Martín Carlos Croci, Diego O. Mariño, Karina V. Rabinovich, Gabriel A. |
| author_role |
author |
| author2 |
Giribaldi, María Laura Blidner, Ada G. Cutine, Anabela M. Gatto, Sabrina G. Morales, Rosa M. Salatino, Mariana Abba, Martín Carlos Croci, Diego O. Mariño, Karina V. Rabinovich, Gabriel A. |
| author2_role |
author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Ciencias Médicas Biología colorectal cancer immune escape Galectin-1 CD8⁺ regulatory T cells |
| topic |
Ciencias Médicas Biología colorectal cancer immune escape Galectin-1 CD8⁺ regulatory T cells |
| dc.description.none.fl_txt_mv |
Colorectal cancer (CRC) represents the third most common malignancy and the second leading cause of cancer-related deaths worldwide. Although immunotherapy has taken center stage in mainstream oncology, it has shown limited clinical efficacy in CRC, generating an urgent need for discovery of new biomarkers and potential therapeutic targets. Galectin-1 (Gal-1), an endogenous glycan-binding protein, induces tolerogenic programs and contributes to tumor cell evasion of immune responses. Here, we investigated the relevance of Gal-1 in CRC and explored its modulatory activity within the CD8⁺ regulatory T cell (Treg) compartment. Mice lacking Gal-1 (Lgals1 -/- ) developed a lower number of tumors and showed a decreased frequency of a particular population of CD8⁺CD122⁺PD-1⁺ Tregs in the azoxymethane-dextran sodium sulfate model of colitis-associated CRC. Moreover, silencing of tumor-derived Gal-1 in the syngeneic CT26 CRC model resulted in reduced number and attenuated immunosuppressive capacity of CD8⁺CD122⁺PD-1⁺ Tregs, leading to slower tumor growth. Moreover, stromal Gal-1 also influenced the fitness of CD8⁺ Tregs, highlighting the contribution of both tumor and stromal-derived Gal-1 to this immunoregulatory effect. Finally, bioinformatic analysis of a colorectal adenocarcinoma from The Cancer Genome Atlas dataset revealed a particular signature characterized by high CD8⁺ Treg score and elevated Gal-1 expression, which delineates poor prognosis in human CRC. Our findings identify CD8⁺CD122⁺PD-1⁺ Tregs as a target of the immunoregulatory activity of Gal-1, suggesting a potential immunotherapeutic strategy for the treatment of CRC. Centro de Investigaciones Inmunológicas Básicas y Aplicadas |
| description |
Colorectal cancer (CRC) represents the third most common malignancy and the second leading cause of cancer-related deaths worldwide. Although immunotherapy has taken center stage in mainstream oncology, it has shown limited clinical efficacy in CRC, generating an urgent need for discovery of new biomarkers and potential therapeutic targets. Galectin-1 (Gal-1), an endogenous glycan-binding protein, induces tolerogenic programs and contributes to tumor cell evasion of immune responses. Here, we investigated the relevance of Gal-1 in CRC and explored its modulatory activity within the CD8⁺ regulatory T cell (Treg) compartment. Mice lacking Gal-1 (Lgals1 -/- ) developed a lower number of tumors and showed a decreased frequency of a particular population of CD8⁺CD122⁺PD-1⁺ Tregs in the azoxymethane-dextran sodium sulfate model of colitis-associated CRC. Moreover, silencing of tumor-derived Gal-1 in the syngeneic CT26 CRC model resulted in reduced number and attenuated immunosuppressive capacity of CD8⁺CD122⁺PD-1⁺ Tregs, leading to slower tumor growth. Moreover, stromal Gal-1 also influenced the fitness of CD8⁺ Tregs, highlighting the contribution of both tumor and stromal-derived Gal-1 to this immunoregulatory effect. Finally, bioinformatic analysis of a colorectal adenocarcinoma from The Cancer Genome Atlas dataset revealed a particular signature characterized by high CD8⁺ Treg score and elevated Gal-1 expression, which delineates poor prognosis in human CRC. Our findings identify CD8⁺CD122⁺PD-1⁺ Tregs as a target of the immunoregulatory activity of Gal-1, suggesting a potential immunotherapeutic strategy for the treatment of CRC. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021-05 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Articulo http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://sedici.unlp.edu.ar/handle/10915/146467 |
| url |
http://sedici.unlp.edu.ar/handle/10915/146467 |
| dc.language.none.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/issn/1091-6490 info:eu-repo/semantics/altIdentifier/issn/0027-8424 info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.2102950118 info:eu-repo/semantics/altIdentifier/pmid/34006646 |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/4.0/ Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) |
| eu_rights_str_mv |
openAccess |
| rights_invalid_str_mv |
http://creativecommons.org/licenses/by-nc-nd/4.0/ Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.source.none.fl_str_mv |
reponame:SEDICI (UNLP) instname:Universidad Nacional de La Plata instacron:UNLP |
| reponame_str |
SEDICI (UNLP) |
| collection |
SEDICI (UNLP) |
| instname_str |
Universidad Nacional de La Plata |
| instacron_str |
UNLP |
| institution |
UNLP |
| repository.name.fl_str_mv |
SEDICI (UNLP) - Universidad Nacional de La Plata |
| repository.mail.fl_str_mv |
alira@sedici.unlp.edu.ar |
| _version_ |
1846783501587709952 |
| score |
12.618931 |