Primary central nervous system diffuse large B-cell lymphoma has poorer immune cell infiltration and prognosis than its peripheral counterpart

Histopathology. 2015 Nov;67(5):625-35. doi: 10.1111/his.12706. Epub 2015 May 19.

Abstract

Aims: Primary central nervous system (CNS) diffuse large B-cell lymphoma (PCNSL) is an ominous disease with a poor prognosis. The brain is an immune-privileged sanctuary, and this may contribute to an ineffective host immune response and thus a poorer outcome. The aim of this study was therefore to study the difference in the immune composition in PCNSL and non-CNS diffuse large B-cell lymphoma (DLBCL), and the role of the immune response in PCNSL prognosis.

Methods and results: Thirty-two biopsy specimens of PCNSL and 30 specimens of low-stage non-CNS DLBCL from immunocompetent patients formed the study group. The density and distribution of immune cells, including dendritic cells (dendritic cell-specific lysosomal-associated membrane protein-positive and S100-positive), effector/memory T cells (CD45RO-positive), and cytotoxic T cells (granzyme B-positive), and the expression of HLA-DR by lymphoma cells, were evaluated immunohistochemically. PCNSL patients showed poorer overall survival (P = 0.032). On comparison of the PCNSL and DLBCL biopsy specimens, the PCNSL cells showed less HLA-DR expression (P = 0.003), and there were fewer S100-positive cells (P < 0.01), and effector T cells (P = 0.026) infiltrating PCNSL than infiltrating DLBCL. For PCNSL patients, fewer cytotoxic T cells in the background constituted a poor prognostic factor (P = 0.004). Intratumoral S100-positive cell infiltration was positively correlated with T-cell infiltration, and a T-cell rimming pattern.

Conclusions: In PCNSL, the baseline antitumour immune response is less as compared with non-CNS DLBCL, and this response may play a role in the poorer prognosis. Adjuvant dendritic cell and T-cell immunotherapy may further boost treatment responses in PCNSL patients.

Keywords: T cells; antitumour immunity; dendritic cells; diffuse large B-cell lymphoma; primary central nervous system; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Central Nervous System Neoplasms / immunology
  • Central Nervous System Neoplasms / mortality
  • Central Nervous System Neoplasms / pathology*
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphoma, Large B-Cell, Diffuse / immunology*
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Lymphoma, Large B-Cell, Diffuse / pathology*
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Young Adult