Correction: critical role for sec22b-dependent antigen cross-presentation in antitumor immunity

The authors regret that in the original version of their paper, they mistakenly used the phrase OVA-expressing cells instead of OVA-secreting cells in parts of the text and cited reference Boissonnas et al. (2007. http://dx.doi.org/10.1084/jem.20061890) instead of Zeelenberg et al. (2008. http://dx.doi.org/10.1158/0008-5472.CAN-07-3163) and Sedlik et al. (2014. http://dx.doi.org/10.3402/jev.v3.24646). The Results and discussion paragraph containing the corrected references and full bibliographic information appear below.Fil: Alloatti, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Rookhuizen, Derek C.. Institute Curie. U-932 Immunity And Cancer; FranciaFil: Joannas, Leonel. Institute Curie. U-932 Immunity And Cancer; FranciaFil: Carpier, Jean-Marie. Institute Curie. U-932 Immunity And Cancer; FranciaFil: Iborra, Salvador. Institute Curie. U-932 Immunity And Cancer; FranciaFil: Magalhaes, Joao G.. Institute Curie. U-932 Immunity And Cancer; FranciaFil: Yatim, Nader. Institut Pasteur, Paris; FranciaFil: Kozik, Patrycja. Institute Curie. U-932 Immunity And Cancer; FranciaFil: Sancho, David. Institute Curie. U-932 Immunity And Cancer; FranciaFil: Albert, Matthew L.. Institut Pasteur, Paris; FranciaFil: Amigorena, Sebastian. Institute Curie. U-932 Immunity And Cancer; Franci

Epigenetically controlled tumor antigens derived from splice junctions between exons and transposable elements

Oncogenesis often implicates epigenetic alterations, including derepression of transposable elements (TEs) and defects in alternative splicing. Here, we explore the possibility that noncanonical splice junctions between exons and TEs represent a source of tumor-specific antigens. We show that mouse normal tissues and tumor cell lines express wide but distinct ranges of mRNA junctions between exons and TEs, some of which are tumor specific. Immunopeptidome analyses in tumor cell lines identified peptides derived from exon-TE splicing junctions associated to MHC-I molecules. Exon-TE junction-derived peptides were immunogenic in tumor-bearing mice. Both prophylactic and therapeutic vaccinations with junction-derived peptides delayed tumor growth in vivo. Inactivation of the TE-silencing histone 3-lysine 9 methyltransferase Setdb1 caused overexpression of new immunogenic junctions in tumor cells. Our results identify exon-TE splicing junctions as epigenetically controlled, immunogenic, and protective tumor antigens in mice, opening possibilities for tumor targeting and vaccination in patients with cancer

Extracellular vesicles from triple negative breast cancer promote pro-inflammatory macrophages associated with better clinical outcome

International audienceTumor associated macrophages (TAMs), which differentiate from circulating monocytes, are pervasive across human cancers and comprise heterogeneous populations. The contribution of tumor-derived signals to TAM heterogeneity is not well understood. In particular, tumors release both soluble factors and extracellular vesicles (EVs), whose respective impact on TAM precursors may be different. Here, we show that triple negative breast cancer cells (TNBCs) release EVs and soluble molecules promoting monocyte differentiation toward distinct macrophage fates. EVs specifically promoted proinflammatory macrophages bearing an interferon response signature. The combination in TNBC EVs of surface CSF-1 promoting survival and cargoes promoting cGAS/STING or other activation pathways led to differentiation of this particular macrophage subset. Notably, macrophages expressing the EV-induced signature were found among patients’ TAMs. Furthermore, higher expression of this signature was associated with T cell infiltration and extended patient survival. Together, this data indicates that TNBC-released CSF-1-bearing EVs promote a tumor immune microenvironment associated with a better prognosis in TNBC patients