Abstract

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.

Details

Title
The C-type lectin DCIR contributes to the immune response and pathogenesis of colorectal cancer
Author
Trimaglio, Giulia 1 ; Sneperger, Tamara 1 ; Raymond, Benjamin B. A. 1 ; Gilles, Nelly 1 ; Näser, Emmanuelle 1 ; Locard-Paulet, Marie 1 ; Ijsselsteijn, Marieke E. 2 ; Brouwer, Thomas P. 2 ; Ecalard, Romain 3 ; Roelands, Jessica 2 ; Matsumoto, Naoki 4 ; Colom, André 1 ; Habch, Myriam 1 ; de Miranda, Noel F. C. C. 2 ; Vergnolle, Nathalie 5 ; Devaud, Christel 5 ; Neyrolles, Olivier 1 ; Rombouts, Yoann 1 

 Université de Toulouse, CNRS, UPS, Institut de Pharmacologie et de Biologie Structurale, IPBS, Toulouse, France (GRID:grid.15781.3a) (ISNI:0000 0001 0723 035X) 
 Leiden University Medical Center, Department of Pathology, Leiden, The Netherlands (GRID:grid.10419.3d) (ISNI:0000 0000 8945 2978) 
 Purpan Hospital, INSERM US006 ANEXPLO/CREFRE, Toulouse, France (GRID:grid.414282.9) (ISNI:0000 0004 0639 4960) 
 The University of Tokyo, Department of Integrated Biosciences, Graduate School of Frontier Sciences, Kashiwa, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X) 
 Université de Toulouse, INSERM, INRAe, ENVT, UPS, Institut de Recherche en Santé Digestive, IRSD, Toulouse, France (GRID:grid.15781.3a) (ISNI:0000 0001 0723 035X) 
Pages
7199
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2986724499
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.