RT Journal Article
SR Electronic
T1 cDC1 and interferons promote spontaneous CD4<sup>+</sup> and CD8<sup>+</sup> T cell protective responses to breast cancer
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.23.424092
DO 10.1101/2020.12.23.424092
A1 Raphaël Mattiuz
A1 Carine Brousse
A1 Marc Ambrosini
A1 Jean-Charles Cancel
A1 Gilles Bessou
A1 Julie Mussard
A1 Amélien Sanlaville
A1 Christophe Caux
A1 Nathalie Bendriss-Vermare
A1 Jenny Valladeau-Guilemond
A1 Marc Dalod
A1 Karine Crozat
YR 2020
UL http://biorxiv.org/content/early/2020/12/24/2020.12.23.424092.abstract
AB Here we show that efficient breast cancer immunosurveillance relies on cDC1, conventional CD4+ T cells, CD8+ cytotoxic T lymphocytes (CTL) and later NK/NK T cells. For this process, cDC1 were required constitutively, but especially during the T cell priming phase. In the tumor microenvironment, cDC1 interacted physically and jointly with both CD4+ T cells and tumorspecific CD8+ T cells. We found that interferon (IFN) responses were necessary for the rejection of breast cancer, including cDC1-intrinsic signaling by IFN-γ and STAT1. Surprisingly, cell-intrinsic IFN-I signaling in cDC1 was not required. cDC1 and IFNs shaped the tumor immune landscape, notably by promoting CD4+ and CD8+ T cell infiltration, terminal differentiation and effector functions. XCR1, CXCL9, IL-12 and IL-15 were individually dispensable for breast cancer immunosurveillance. Consistent with our experimental results in mice, high expression in the tumor microenvironment of genes specific to cDC1, CTL, helper T cells or interferon responses are associated with a better prognosis in human breast cancer patients. Our results show that immune control of breast cancer depends on cDC1 and IFNs as previously reported for immunogenic melanoma or fibrosarcoma tumor models, but that the underlying mechanism differ. Revisiting cDC1 functions in the context of spontaneous immunity to cancer should help defining new ways to mobilize cDC1 functions to improve already existing immunotherapies for the benefits of patients.Synopsis Type 1 conventional dendritic cells cross-present tumor antigens to CD8+ T cells. Understanding the regulation of their antitumor functions is important. Cell-intrinsic STAT1/IFN-γ signaling licenses them for efficient CD4+ and CD8+ T cell activation during breast cancer immunosurveillance.Competing Interest StatementThe authors have declared no competing interest.