CD4 + T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors.

Autor: Lei X; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.; Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands., de Groot DC; Department of Tumor Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Welters MJP; Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands., de Wit T; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.; Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands., Schrama E; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.; Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands., van Eenennaam H; IMMIOS B.V., Oss, The Netherlands., Santegoets SJ; Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands., Oosenbrug T; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands., van der Veen A; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands., Vos JL; Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Zuur CL; Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.; Department of Otorhinolaryngology Leiden University Medical Center, Leiden, The Netherlands., de Miranda NFCC; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands., Jacobs H; Department of Tumor Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., van der Burg SH; Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands.; Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands., Borst J; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands. j.g.borst@lumc.nl.; Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands. j.g.borst@lumc.nl., Xiao Y; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands. y.xiao@lumc.nl.; Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands. y.xiao@lumc.nl.
Jazyk: angličtina
Zdroj: Cellular & molecular immunology [Cell Mol Immunol] 2024 Apr; Vol. 21 (4), pp. 374-392. Date of Electronic Publication: 2024 Feb 21.
DOI: 10.1038/s41423-024-01133-1
Abstrakt: CD4 + T cells can "help" or "license" conventional type 1 dendritic cells (cDC1s) to induce CD8 + cytotoxic T lymphocyte (CTL) anticancer responses, as proven in mouse models. We recently identified cDC1s with a transcriptomic imprint of CD4 + T-cell help, specifically in T-cell-infiltrated human cancers, and these cells were associated with a good prognosis and response to PD-1-targeting immunotherapy. Here, we delineate the mechanism of cDC1 licensing by CD4 + T cells in humans. Activated CD4 + T cells produce IFNβ via the STING pathway, which promotes MHC-I antigen (cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer responses. In cooperation with CD40 ligand (L), IFNβ also optimizes the costimulatory and other functions of cDC1s required for CTL response induction. IFN-I-producing CD4 + T cells are present in diverse T-cell-infiltrated cancers and likely deliver "help" signals to CTLs locally, according to their transcriptomic profile and colocalization with "helped/licensed" cDCs and tumor-reactive CD8 + T cells. In agreement with this scenario, the presence of IFN-I-producing CD4 + T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.
(© 2024. The Author(s).)
Databáze: MEDLINE
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