Chen Chang1, Ching-Hung Lin2, Ann-Lii Cheng2, L Jeffrey Medeiros3, Kung-Chao Chang1. 1. Department of Pathology, College of Medicine, National Cheng Kung University and Hospital, Tainan, Taiwan. 2. Departments of Oncology and Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. 3. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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.
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.