Poster Presentation 14th Lorne Infection and Immunity 2024

Immune cell infiltration of testicular germ cell tumors – what is known and which questions are unanswered so far? (#133)

Rashidul Islam 1 2 3 , Miriam Figura 1 4 , Jannis Heyer 1 4 , Florian Dittmar 4 , Benedict Nathaniel 2 , Katja Hartmann 1 , Christiane Pleuger 5 , Monika Fijak 5 , Sabine Kliesch 6 , Adrian Pilatz 4 , Florian Wagenlehner 4 , Mark Hedger 2 , Bruce Loveland 7 , Kate Loveland 2 3 , Hans-Christian Schuppe 4 , Daniela Fietz 1
  1. Department of Veterinary Anatomy, Histology and Embryology, Justus Liebig University Giessen, Giessen, Germany
  2. Centre for Reproductive Health, Hudson Institute for Medical Research, Clayton , Victoria, Australia
  3. School of Clinical Sciences, Monash University, Clayton , Victoria, Australia
  4. Dept. of Urology, Pediatric Urology and Andrology, Justus Liebig University , Giessen, Germany
  5. Institute of Anatomy and Cell Biology, Justus Liebig University, Giessen, Germany
  6. Centre of Reproductive Medicine and Andrology, University of Muenster, Muenster, Germany
  7. Burnet Institute, Melbourne, Australia

Testicular germ cell tumors (TGCT) are the most common tumors in young men (14-44 years) and mostly present as seminoma (SE) and embryonic carcinoma (EC), both arising from germ cell neoplasia in situ (GCNIS). TGCTs are thought to “hjack” the immune system to favor their development, using the anti-inflammatory environment of the immune-privileged testis. Besides e.g. macrophages, T cells are the major component of tumor infiltrating lymphocytes; subtypes such as regulatory (Treg) or follicular helper T cells (Tfh) had not yet been analysed.

We used retrospective and prospective patient cohorts to categorise immune cells in TGCT compared to controls. Immunohistochemistry (IHC) was performed on SE (n=75), EC (n=26), GCNIS (n=30), preserved spermatogenesis (NSP, n=10), and testicular inflammation (n=12), with flow cytometry (FC) on SE (n=12) and EC (n=6) using markers for macrophages, dendritic cells (DC), T and B cells. We showed that the immune cell environment is shifted from (resident) macrophages in NSP to (newly recruited) T cells in TGCTs. Treg and Tfh were most abundant in central parts of SE. Comparing SE and EC, SE (n=33) contained mostly T cells and macrophages whereas in EC tumor-samples (n=10), mostly T cells and DCs were detected. In SE, follicular like structures contained clusters of B cells and Tfh.

This study describes the complexity of immune cells in TGCTs by characterising SE and EC patterns, and provides first indications of a potential importance of rarer T cell subtypes in the immune environment of TGCT. The prospective clinical database will allow correlations between immune cell patterns and clinical parameters, e.g. localised and metastatic TGCTs. With this comprehensive approach, we aim to decipher the role of "immune editing" during TGCT development, progression and possible metastatic behaviour. Results will help to identify novel prognostic factors and immune-therapeutic concepts in human TGCTs. Funded by DFG GRK1871/2.