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@ARTICLE{Lei:210385,
      author       = {X. Lei and I. Khatri and T. de Wit and I. de Rink and M.
                      Nieuwland and R. Kerkhoven and H. van Eenennaam and C.
                      Sun$^*$ and A. D. Garg and J. Borst and Y. Xiao},
      title        = {{CD}4+ helper {T} cells endow c{DC}1 with cancer-impeding
                      functions in the human tumor micro-environment.},
      journal      = {Nature Communications},
      volume       = {14},
      number       = {1},
      issn         = {2041-1723},
      address      = {[London]},
      publisher    = {Nature Publishing Group UK},
      reportid     = {DKFZ-2023-00114},
      pages        = {217},
      year         = {2023},
      abstract     = {Despite their low abundance in the tumor microenvironment
                      (TME), classical type 1 dendritic cells (cDC1) play a
                      pivotal role in anti-cancer immunity, and their abundance
                      positively correlates with patient survival. However, their
                      interaction with CD4+ T-cells to potentially enable the
                      cytotoxic T lymphocyte (CTL) response has not been
                      elucidated. Here we show that contact with activated CD4+
                      T-cells enables human ex vivo cDC1, but no other DC types,
                      to induce a CTL response to cell-associated tumor antigens.
                      Single cell transcriptomics reveals that CD4+ T-cell help
                      uniquely optimizes cDC1 in many functions that support
                      antigen cross-presentation and T-cell priming, while these
                      changes don't apply to other DC types. We robustly identify
                      'helped' cDC1 in the TME of a multitude of human cancer
                      types by the overlap in their transcriptomic signature with
                      that of recently defined, tumor-infiltrating DC states that
                      prove to be positively prognostic. As predicted from the
                      functional effects of CD4+ T-cell help, the transcriptomic
                      signature of 'helped' cDC1 correlates with tumor
                      infiltration by CTLs and Thelper(h)-1 cells, overall
                      survival and response to PD-1-targeting immunotherapy. These
                      findings reveal a critical role for CD4+ T-cell help in
                      enabling cDC1 function in the TME and may establish the
                      helped cDC1 transcriptomic signature as diagnostic marker in
                      cancer.},
      keywords     = {Humans / CD8-Positive T-Lymphocytes / Neoplasms: metabolism
                      / Antigen Presentation / T-Lymphocytes, Cytotoxic /
                      Dendritic Cells / T-Lymphocytes, Helper-Inducer: metabolism
                      / Tumor Microenvironment},
      cin          = {D250},
      ddc          = {500},
      cid          = {I:(DE-He78)D250-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36639382},
      pmc          = {pmc:PMC9839676},
      doi          = {10.1038/s41467-022-35615-5},
      url          = {https://inrepo02.dkfz.de/record/210385},
}