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P03.03 Organization, function and gene expression of tertiary lymphoid structures in PDAC resembles lymphoid follicles in secondary lymphoid organs
  1. M Thelen1,
  2. MA García-Márquez1,
  3. T Nestler2,
  4. S Wagener-Ryczek2,
  5. J Lehmann1,
  6. E Staib1,
  7. F Popp3,
  8. F Gebauer3,
  9. P Lohneis2,
  10. M Odenthal2,
  11. S Merkelbach-Bruse2,
  12. C Bruns3,
  13. K Wennhold1,
  14. M von Bergwelt-Baildon4 and
  15. HA Schlößer1,3
  1. 1Center for Molecular Medicine Cologne, University Hospital of Cologne, Cologne, Germany
  2. 2Institute for Pathology, University Hospital of Cologne, Cologne, Germany
  3. 3Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne, Germany
  4. 4Department of Internal Medicine III, Ludwig Maximilian University Munich, Munich, Germany


Background Secondary lymphoid organs (SLO) are involved in induction and enhancement of anti-tumor immune responses on different tumor entities. Recent evidence suggests that anti-tumor immune responses may also be induced or enhanced in the tumor microenvironment in so called tertiary lymphoid structures (TLS). It is assumed that TLS represent a hotspot for T cell priming, B cell activation, and differentiation, leading to cellular and humoral anti-tumor immune response.

Methods FFPE-slides of 120 primary pancreatic ductal adenocarcinoma (PDAC) patients were immunohistochemically (IHC) stained for CD20, CD3, CD8 and HLA-ABC to analyze spatial distribution of tumor-infiltrating lymphocytes. 5-color immunofluorescence staining was performed to further investigate structural components of TLS in comparison to lymphoid follicles in SLOs. Microscope-based laser microdissection and Nanostring-base RNA expression analysis were used to compare gene expression in PDAC, TLS, SLOs and normal pancreatic tissue.

Results TLS were frequently detected in PDAC and were mainly localized along the invasive tumor margin. In less than 10% of the cases TLS were infiltrating the tumors. Interestingly, 20% of the patients had no TLS. Results of TLS will be correlated with clinical parameters, Immunoscore and immune escape mechanisms. 5-color Immunofluorescence staining revealed similar organization and function of TLS and SLO. Finally, gene expression analyzed by Nanostring revealed largely overlapping expression patterns in TLS and SLO.

Conclusions The results clearly demonstrate close similarities between SLO and TLS in terms of composition, distribution and gene expression Patterns.

Disclosure Information M. Thelen: None. M.A. García-Márquez: None. T. Nestler: None. S. Wagener-Ryczek: None. J. Lehmann: None. E. Staib: None. F. Popp: None. F. Gebauer: None. P. Lohneis: None. M. Odenthal: None. S. Merkelbach-Bruse: None. C. Bruns: None. K. Wennhold: None. M. von Bergwelt-Baildon: None. H.A. Schlößer: None.

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