The C-type lectin DCIR contributes to the immune response and pathogenesis of colorectal cancer

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...

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Published in:	Scientific reports Vol. 14; no. 1; p. 7199
Main Authors:	Trimaglio, Giulia, Sneperger, Tamara, Raymond, Benjamin B. A., Gilles, Nelly, Näser, Emmanuelle, Locard-Paulet, Marie, Ijsselsteijn, Marieke E., Brouwer, Thomas P., Ecalard, Romain, Roelands, Jessica, Matsumoto, Naoki, Colom, André, Habch, Myriam, de Miranda, Noel F. C. C., Vergnolle, Nathalie, Devaud, Christel, Neyrolles, Olivier, Rombouts, Yoann
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 26-03-2024 Nature Publishing Group Nature Portfolio
Subjects:	631/250/580 631/45/221 631/67/1504/1885 631/67/70 Animal models C-type lectin Cancer CD4 antigen CD8 antigen Cellular Biology Colorectal cancer Colorectal carcinoma Dendritic cell immunoreceptor Dendritic cells Food and Nutrition Gene expression Homeostasis Human health and pathology Humanities and Social Sciences Immune response Immunoregulation Immunotherapy Inflammation Life Sciences Lymphocytes T Macrophages Malignancy Microenvironments multidisciplinary Myeloid cells Phenotypes Science Science (multidisciplinary) Tissues and Organs Toxicology Toxicology and food chain Transcriptomics Tumor microenvironment Tumors Immune response Tumor microenvironment Dendritic cell immunoreceptor Colorectal cancer C-type lectin
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-024-57941-y