Article Text

Download PDFPDF

Phenotype, function and T cell receptor repertoire of tumor-infiltrating lymphocytes in patients with pancreatic ductal adenocarcinoma
  1. Isabel Poschke1,
  2. Michael Flossdorf1,
  3. Marta Faryna2,
  4. Frank Bergmann3,
  5. Jessica Hassel3,
  6. Oliver Strobel1 and
  7. Rienk Offringa1
  1. Aff1 grid.7497.d0000000404920584German Cancer Research Center (DKFZ) Heidelberg Germany
  2. Aff2 3BioNTech Diagnostics GmBH Mainz Germany
  3. Aff3 grid.5253.10000000103284908Heidelberg University Hospital Heidelberg Germany

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Meeting abstracts


Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a median survival of only about two years even in the 20% of patients that present early enough to be eligible for surgical resection and adjuvant chemotherapy. With this urgent medical need in mind, we are exploring the use of adoptive T cell transfer in patients with PDAC, as this therapy has shown remarkable clinical success in patients with advanced melanoma.


Despite the notion that, different from melanoma, PDAC is a non-immunogenic tumor, we observe at least moderate (>150 CD3+cells/mm2) T cell infiltration in 60% of patient biopsies analyzed by immunohistochemistry (n=66). Flow cytometric analysis shows that tumor-infiltrating T lymphocytes (TILs) predominantly display an activated effector memory phenotype with signs of exhaustion or prolonged antigen exposure, such as high PD1 (n≥30).

Upon in vitro culture TILs can be expanded from 85% of PDAC patients (n=96) and show growth capacity and phenotypes similar to melanoma patient TIL (n=62). The majority of tested PDAC TIL cultures produce IFN-γ in response to autologous tumor cells in an MHC-I dependent manner, but cross-reactivity and a low response magnitude are common observations.

In order to gain insight into the original tumor-reactivity of TILs before expansion, we studied the T cell receptor (TCR) repertoire by deep sequencing and made the following observations: the TIL TCR repertoire is i) distinct from the broad repertoire observed in the blood; ii) usually dominated by large T cell clones, possibly due to in situ expansion after tumor-antigen encounter; and iii) in most patients not maintained during the TIL expansion period, likely leading to a loss of important T cell clones and a shift in tumor-reactivity in the TILs available for patient treatment after in vitro expansion.

Deep sequencing of the TCR repertoire in combination with TCR cloning provides us with a tool to study TIL reactivity directly ex vivo and to ‘rescue’ TIL-TCRs with valuable reactivities that could be reintroduced in the form of genetically engineered T cells. Whether PDAC TILs are reactive towards shared antigens and/or mutation-derived neo-antigens is currently being investigated based on exome and RNA sequencing data from a subset of patients.