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@ARTICLE{Lehmann:299521,
      author       = {J. Lehmann and M. Thelen and C. Kreer and S. Schran and M.
                      A. Garcia-Marquez and I. Cisic and K. Siepmann and E. M.
                      Hagen and H. N. C. Eckel and P. Lohneis and S. Kruger and S.
                      Boeck and S. Ormanns and M. Rudelius and J. Werner and F.
                      Popp and F. Klein and M. S. von Bergwelt-Baildon$^*$ and C.
                      J. Bruns and A. Quaas and K. Wennhold and H. A. Schlößer},
      title        = {{T}ertiary {L}ymphoid {S}tructures in {P}ancreatic {C}ancer
                      are {S}tructurally {H}omologous, {S}hare {G}ene {E}xpression
                      {P}atterns and {B}-cell {C}lones with {S}econdary {L}ymphoid
                      {O}rgans, but {S}how {I}ncreased {T}-cell {A}ctivation.},
      journal      = {Cancer immunology research},
      volume       = {13},
      number       = {3},
      issn         = {2326-6066},
      address      = {Philadelphia, Pa.},
      publisher    = {AACR},
      reportid     = {DKFZ-2025-00479},
      pages        = {323 - 336},
      year         = {2025},
      abstract     = {Tertiary lymphoid structures (TLS) in cancer are considered
                      ectopic hotspots for immune activation that are similar to
                      lymphoid follicles in secondary lymphoid organs (SLO). This
                      study elucidates shared and TLS/SLO-specific features in
                      pancreatic ductal adenocarcinoma (PDAC). TLS abundance was
                      related to superior survival and T-cell abundance in 110
                      treatment-naïve PDAC samples, underlining their clinical
                      relevance. Immunofluorescence microscopy identified
                      structural homologies between TLSs and SLOs. In RNA
                      expression analyses of laser-microdissected TLSs and paired
                      SLOs, we observed largely overlapping expression patterns of
                      immune-related gene clusters but distinct expression
                      patterns of T-cell and complement-associated genes. Immune
                      cells in TLS expressed essential markers of germinal center
                      formation. Increased activation of tumor-draining lymph
                      nodes in patients with high numbers of TLSs highlights the
                      relevance of these tumor-related structures to systemic
                      immune response. In line with this, we identified an overlap
                      of expanded B-cell receptor clonotypes in TLSs and SLOs,
                      which suggests a vivid cross-talk between the two
                      compartments. We conclude that combined therapeutic
                      approaches exploiting TLS-mediated antitumor immune
                      responses may improve susceptibility of PDAC to
                      immunotherapy.},
      keywords     = {Humans / Tertiary Lymphoid Structures: immunology /
                      Pancreatic Neoplasms: immunology / Pancreatic Neoplasms:
                      pathology / Pancreatic Neoplasms: genetics / Pancreatic
                      Neoplasms: metabolism / B-Lymphocytes: immunology /
                      B-Lymphocytes: metabolism / T-Lymphocytes: immunology /
                      T-Lymphocytes: metabolism / Lymphocyte Activation:
                      immunology / Carcinoma, Pancreatic Ductal: immunology /
                      Carcinoma, Pancreatic Ductal: pathology / Carcinoma,
                      Pancreatic Ductal: genetics / Male / Female / Aged / Middle
                      Aged / Gene Expression Regulation, Neoplastic / Gene
                      Expression Profiling},
      cin          = {MU01},
      ddc          = {610},
      cid          = {I:(DE-He78)MU01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39661055},
      doi          = {10.1158/2326-6066.CIR-24-0299},
      url          = {https://inrepo02.dkfz.de/record/299521},
}