Haematologica (Feb 2019)

T-cell inflamed tumor microenvironment predicts favorable prognosis in primary testicular lymphoma

  • Suvi-Katri Leivonen,
  • Marjukka Pollari,
  • Oscar Brück,
  • Teijo Pellinen,
  • Matias Autio,
  • Marja-Liisa Karjalainen-Lindsberg,
  • Susanna Mannisto,
  • Pirkko-Liisa Kellokumpu-Lehtinen,
  • Olli Kallioniemi,
  • Satu Mustjoki,
  • Sirpa Leppä

DOI
https://doi.org/10.3324/haematol.2018.200105
Journal volume & issue
Vol. 104, no. 2

Abstract

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Primary testicular lymphoma is a rare lymphoid malignancy, most often, histologically, representing diffuse large B-cell lymphoma. The tumor microenvironment and limited immune surveillance have a major impact on diffuse large B-cell lymphoma pathogenesis and survival, but the impact on primary testicular lymphoma is unknown. Here, the purpose of the study was to characterize the tumor microenvironment in primary testicular lymphoma, and associate the findings with outcome. We profiled the expression of 730 immune response genes in 60 primary testicular lymphomas utilizing the Nanostring platform, and used multiplex immunohistochemistry to characterize the immune cell phenotypes in the tumor tissue. We identified a gene signature enriched for T-lymphocyte markers differentially expressed between the patients. Low expression of the signature predicted poor outcome independently of the International Prognostic Index (progression-free survival: HR=2.810, 95%CI: 1.228-6.431, P=0.014; overall survival: HR=3.267, 95%CI: 1.406-7.590, P=0.006). The T-lymphocyte signature was associated with outcome also in an independent diffuse large B-cell lymphoma cohort (n=96). Multiplex immunohistochemistry revealed that poor survival of primary testicular lymphoma patients correlated with low percentage of CD3+CD4+ and CD3+CD8+ tumor-infiltrating lymphocytes (P