气候变化领域集成服务门户(CCPortal): Galectin-1 fosters an immunosuppressive microenvironment in colorectal cancer by reprogramming CD8+ regulatory T cells

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DOI	10.1073/pnas.2102950118
	Galectin-1 fosters an immunosuppressive microenvironment in colorectal cancer by reprogramming CD8+ regulatory T cells
	Cagnoni A.J.; Giribaldi M.L.; Blidner A.G.; Cutine A.M.; Gatto S.G.; Morales R.M.; Salatino M.; Abba M.C.; Croci D.O.; Mariño K.V.; Rabinovich G.A.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:21
英文摘要	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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	CD8+ regulatory T cells; Colorectal cancer; Galectin-1; immune escape
语种	英语
scopus关键词	galectin 1; interleukin 2 receptor beta; programmed death 1 receptor; azoxymethane; dextran sulfate; galectin 1; IL2RB protein, human; interleukin 2 receptor beta; LGALS1 protein, human; Lgals1 protein, mouse; PDCD1 protein, human; programmed death 1 receptor; animal cell; animal experiment; animal model; Article; bioinformatics; C57BL 6 mouse; cancer inhibition; cancer prognosis; CD8+ T lymphocyte; clinical outcome; cohort analysis; colitis; colorectal cancer; controlled study; CT26 cell line; immunosuppressive treatment; in vivo study; modulation; mouse; nonhuman; nuclear reprogramming; regulatory T lymphocyte; tumor immunity; tumor microenvironment; adenocarcinoma; animal; biology; book; CD8+ T lymphocyte; colorectal tumor; disease model; gene expression regulation; genetics; human; immunology; knockout mouse; mortality; pathology; regulatory T lymphocyte; signal transduction; survival analysis; tumor cell line; tumor volume; Adenocarcinoma; Animals; Atlases as Topic; Azoxymethane; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Colitis; Colorectal Neoplasms; Computational Biology; Dextran Sulfate; Disease Models, Animal; Galectin 1; Gene Expression Regulation, Neoplastic; Humans; Interleukin-2 Receptor beta Subunit; Mice; Mice, Knockout; Programmed Cell Death 1 Receptor; Signal Transduction; Survival Analysis; T-Lymphocytes, Regulatory; Tumor Burden
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251176
作者单位	Laboratorio de Glicómica Funcional y Molecular, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, C1428ADN, Argentina; Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, C1428ADN, Argentina; Centro de Investigaciones Inmunológicas Básicas y Aplicadas, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, C1900, Argentina; Laboratorio de Inmunopatología, Instituto de Histología y Embriología de Mendoza, Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo, Mendoza, M5500, Argentina; Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, C1428EGA, Argentina; Laboratorio de Inmuno-Oncología Traslacional, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Bue...
推荐引用方式 GB/T 7714	Cagnoni A.J.,Giribaldi M.L.,Blidner A.G.,et al. Galectin-1 fosters an immunosuppressive microenvironment in colorectal cancer by reprogramming CD8+ regulatory T cells[J],2021,118(21).
APA	Cagnoni A.J..,Giribaldi M.L..,Blidner A.G..,Cutine A.M..,Gatto S.G..,...&Rabinovich G.A..(2021).Galectin-1 fosters an immunosuppressive microenvironment in colorectal cancer by reprogramming CD8+ regulatory T cells.Proceedings of the National Academy of Sciences of the United States of America,118(21).
MLA	Cagnoni A.J.,et al."Galectin-1 fosters an immunosuppressive microenvironment in colorectal cancer by reprogramming CD8+ regulatory T cells".Proceedings of the National Academy of Sciences of the United States of America 118.21(2021).