CLEC-1 is a death sensor that limits antigen cross-presentation by dendritic cells and represents a target for cancer immunotherapy.

Autor: Drouin M; OSE Immunotherapeutics, Nantes, France.; Nantes Université, INSERM, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France., Saenz J; Nantes Université, INSERM, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France., Gauttier V; OSE Immunotherapeutics, Nantes, France., Evrard B; Nantes Université, INSERM, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France., Teppaz G; OSE Immunotherapeutics, Nantes, France., Pengam S; OSE Immunotherapeutics, Nantes, France., Mary C; OSE Immunotherapeutics, Nantes, France., Desselle A; OSE Immunotherapeutics, Nantes, France., Thepenier V; OSE Immunotherapeutics, Nantes, France., Wilhelm E; OSE Immunotherapeutics, Nantes, France., Merieau E; Nantes Université, INSERM, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France., Ligeron C; Nantes Université, INSERM, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France., Girault I; OSE Immunotherapeutics, Nantes, France., Lopez MD; Nantes Université, INSERM, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France., Fourgeux C; Nantes Université, INSERM, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France., Sinha D; Nantes Université, INSERM, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France., Baccelli I; OSE Immunotherapeutics, Nantes, France., Moreau A; Nantes Université, INSERM, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France., Louvet C; Nantes Université, INSERM, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France., Josien R; Nantes Université, INSERM, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France.; CHU Nantes, Nantes Université, Laboratoire d'Immunologie, CIMNA, Nantes, France., Poschmann J; Nantes Université, INSERM, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France., Poirier N; OSE Immunotherapeutics, Nantes, France., Chiffoleau E; Nantes Université, INSERM, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2022 Nov 16; Vol. 8 (46), pp. eabo7621. Date of Electronic Publication: 2022 Nov 18.
DOI: 10.1126/sciadv.abo7621
Abstrakt: Tumors exploit numerous immune checkpoints, including those deployed by myeloid cells to curtail antitumor immunity. Here, we show that the C-type lectin receptor CLEC-1 expressed by myeloid cells senses dead cells killed by programmed necrosis. Moreover, we identified Tripartite Motif Containing 21 (TRIM21) as an endogenous ligand overexpressed in various cancers. We observed that the combination of CLEC-1 blockade with chemotherapy prolonged mouse survival in tumor models. Loss of CLEC-1 reduced the accumulation of immunosuppressive myeloid cells in tumors and invigorated the activation state of dendritic cells (DCs), thereby increasing T cell responses. Mechanistically, we found that the absence of CLEC-1 increased the cross-presentation of dead cell-associated antigens by conventional type-1 DCs. We identified antihuman CLEC-1 antagonist antibodies able to enhance antitumor immunity in CLEC-1 humanized mice. Together, our results demonstrate that CLEC-1 acts as an immune checkpoint in myeloid cells and support CLEC-1 as a novel target for cancer immunotherapy.
Databáze: MEDLINE
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