Poster Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Cytokine networks in human testis: differential expression patterns associated with neoplasia and disturbed spermatogenesis (#315)

Britta Klein 1 , Hans Christian Schuppe 2 , Wolfgang Weidner 2 , Sabine Kliesch 3 , Sivanjah Indumathy 4 , Mark Hedger 5 , Kate Loveland 4 , Martin Bergmann 1
  1. Department of Veterinary Medicine, Institute of Veterinary Anatomy, -Histology and Embryology, JLU, Gießen, Germany
  2. Department of Urology, Pediatric Urology and Andrology, JLU, Gießen, Germany
  3. Centre of Reproductive Medicine and Andrology, University of Muenster, Muenster, Germany
  4. Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia
  5. MIMR-PHI Institute of Medical Research, Monash University, Melbourne, Australia

Pre-invasive carcinoma in situ (CIS; syn.: testicular intraepithelial neoplasia) and seminomas contain inflammatory infiltrates mainly consisting of lymphocytes. However, the impact of tumor infiltrating immune cells on testicular tumor immunosurveillance, progression and growth is still unknown. The present study tries to elucidate immunopathology, especially cytokine networks, in seminoma and CIS of the human testis in comparison to disturbed spermatogenesis.

Cryopreserved human testicular tissue specimens were grouped according to the analysis of corresponding HE-stained sections: 1) hypospermatogenesis associated with inflammatory infiltrates (ly) [n=12], 2) CIS associated with ly and seminoma samples [n=11]. Measurements of transcripts encoding different cytokines were made using quantitative RT-PCR: 1) pro-inflammatory cytokines (IL-1b, IL-6, IL-17a, TNF-α), 2) anti-inflammatory cytokines (IL-10, TGF-ß1), 3) chemokines (CXCL-10, CXCL-13, CCL-5), 4) cytokines important in T helper cell (Th) type 1 immune responses (IL-2, IFN-γ, IL-12a, IL-12b + IL-1b, IL-6, TNF-α, IL-10), 5) important in Th2 immune responses (IL-4, IL-5, IL-13, IL-23a + IL-10) and 6) cytokines expressed by Th17 cells (IL-17a).

Group 1 shows a significantly higher expression of IL-5, IL-13 and IL-23a compared to group 2, indicating the influence of Th2 and Th17 cells. In group 2, IL-1b, IL-6, TNF-α, CXCL-10, CXCL-13, CCL-5, IL-2 and IFN-γ are significantly higher expressed compared to group 1, indicating pro-inflammatory features and suggesting the involvement of Th1 cells.

Testicular infiltration with lymphocytes reflects a disturbance of the local immune privilege. Our data indicate that in non-cancer samples, immunoregulatory and immunosuppressive factors (derived from Th2/Th17 cells) are important players that could be involved in low-grade autoimmune inflammation, initiated by tubular damage or exogenous factors, i.e. infectious agents. High levels of pro-inflammatory factors (derived from Th1 cells) in cancer samples though lead to the hypothesis, that along with testicular neoplastic processes a specific immune response is initiated for actively controlling further tumour progression.