Deep exploration of the immune infiltrate and outcome prediction in testicular cancer by quantitative multiplexed immunohistochemistry and gene expression profiling

Peter J. Siska*, Romany A.N. Johnpulle, Alice Zhou, Jennifer Bordeaux, Ju Young Kim, Bashar Dabbas, Naveen Dakappagari, Jeffrey C. Rathmell, W. Kimryn Rathmell, Alicia K. Morgans, Justin M. Balko, Douglas B. Johnson

*Corresponding author for this work

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Platinum-based chemotherapy is usually curative for patients with testicular germ cell tumors (TGCT), but a subset of patients experience disease progression and poor clinical outcomes. Here, we tested whether immune profiling of TGCT could identify novel prognostic markers and therapeutic targets for this patient cohort. We obtained primary and metastatic TGCT samples from one center. We performed immune profiling using multiplexed fluorescence immunohistochemistry (FIHC) for T-cell subsets and immune checkpoints, and targeted gene expression profiling (Nanostring nCounter Immune panel). Publically available data sets were used to validate primary sample analyses. Nearly all samples had some degree of T-cell infiltration and immune checkpoint expression. Seminomas were associated with increased CD3+ T-cell infiltration, decreased Regulatory T-cells, increased PD-L1, and increased PD-1/PD-L1 spatial interaction compared with non-seminomas using FIHC. Gene expression profiling confirmed these findings and also demonstrated increased expression of T-cell markers (e.g., IFNγ, and LAG3) and cancer/testis antigens (e.g., PRAME) in seminomas, whereas non-seminomas demonstrated high neutrophil and macrophage gene signatures. Irrespective of histology, advanced TGCT stage was associated with decreased T-cell and NK-cell signatures, while Treg, neutrophil, mast cell and macrophage signatures increased with advanced stage. Importantly, cancer/testis antigen, neutrophil, and CD8+/regulatory T-cell signatures correlated with recurrence free survival. Thus, deep immune characterization of TGCT using IHC and gene expression profiling identified activated T-cell infiltration which correlated with seminoma histology and good prognosis. These results may provide a rationale for testing of anti-PD-1/PD-L1 agents and suggest prognostic markers.

Original languageEnglish (US)
Article numbere1305535
JournalOncoImmunology
Volume6
Issue number4
DOIs
StatePublished - Apr 3 2017

Keywords

  • Immune
  • PD-1/PD-L1
  • non-seminoma
  • seminoma
  • testicular

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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    Siska, P. J., Johnpulle, R. A. N., Zhou, A., Bordeaux, J., Kim, J. Y., Dabbas, B., Dakappagari, N., Rathmell, J. C., Rathmell, W. K., Morgans, A. K., Balko, J. M., & Johnson, D. B. (2017). Deep exploration of the immune infiltrate and outcome prediction in testicular cancer by quantitative multiplexed immunohistochemistry and gene expression profiling. OncoImmunology, 6(4), [e1305535]. https://doi.org/10.1080/2162402X.2017.1305535