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The C-type lectin DCIR contributes to the immune response and pathogenesis of colorectal cancer
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The C-type lectin DCIR contributes to the immune response and pathogenesis of colorectal cancer
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Journal Article
The C-type lectin DCIR contributes to the immune response and pathogenesis of colorectal cancer
2024
Overview
Development and progression of malignancies are accompanied and influenced by alterations in the surrounding immune microenvironment. Understanding the cellular and molecular interactions between immune cells and cancer cells has not only provided important fundamental insights into the disease, but has also led to the development of new immunotherapies. The C-type lectin Dendritic Cell ImmunoReceptor (DCIR) is primarily expressed by myeloid cells and is an important regulator of immune homeostasis, as demonstrated in various autoimmune, infectious and inflammatory contexts. Yet, the impact of DCIR on cancer development remains largely unknown. Analysis of available transcriptomic data of colorectal cancer (CRC) patients revealed that high DCIR gene expression is associated with improved patients’ survival, immunologically \"hot\" tumors and high immunologic constant of rejection, thus arguing for a protective and immunoregulatory role of DCIR in CRC. In line with these correlative data, we found that deficiency of DCIR1, the murine homologue of human DCIR, leads to the development of significantly larger tumors in an orthotopic murine model of CRC. This phenotype is accompanied by an altered phenotype of tumor-associated macrophages (TAMs) and a reduction in the percentage of activated effector CD4 + and CD8 + T cells in CRC tumors of DCIR1 - deficient mice. Overall, our results show that DCIR promotes antitumor immunity in CRC, making it an attractive target for the future development of immunotherapies to fight the second deadliest cancer in the world.
Publisher
Nature Publishing Group,CCSD,Springer Science and Business Media LLC,Nature Publishing Group UK,Nature Portfolio
Subject
/ [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
/ [SDV.BC]Life Sciences [q-bio]/Cellular Biology
/ [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
/ [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
/ [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain
/ Animals
/ Cancer
/ CD8-Positive T-Lymphocytes - metabolism
/ Colorectal Neoplasms - metabolism
/ Dendritic cell immunoreceptor
/ Humanities and Social Sciences
/ Humans
/ Immunity
/ Lectins, C-Type - metabolism
/ Medicine
/ Mice
/ Q
/ R
/ Science
/ Tumors
ISBN
0011954544000
