Chang Chen, Lin Ching-Hung, Cheng Ann-Lii, Medeiros L Jeffrey, Chang Kung-Chao
Department of Pathology, College of Medicine, National Cheng Kung University and Hospital, Tainan, Taiwan.
Departments of Oncology and Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Histopathology. 2015 Nov;67(5):625-35. doi: 10.1111/his.12706. Epub 2015 May 19.
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.
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.
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.
原发性中枢神经系统（CNS）弥漫性大B细胞淋巴瘤（PCNSL）是一种预后不良的凶险疾病。脑是一个免疫特权庇护所，这可能导致宿主免疫反应无效，从而预后更差。因此，本研究的目的是研究PCNSL与非CNS弥漫性大B细胞淋巴瘤（DLBCL）免疫组成的差异，以及免疫反应在PCNSL预后中的作用。
来自免疫功能正常患者的32例PCNSL活检标本和30例低分期非CNS DLBCL标本组成研究组。通过免疫组织化学评估免疫细胞的密度和分布，包括树突状细胞（树突状细胞特异性溶酶体相关膜蛋白阳性和S100阳性）、效应/记忆T细胞（CD45RO阳性）和细胞毒性T细胞（颗粒酶B阳性），以及淋巴瘤细胞HLA-DR的表达。PCNSL患者的总生存期较差（P = 0.032）。比较PCNSL和DLBCL活检标本，PCNSL细胞的HLA-DR表达较少（P = 0.003），浸润PCNSL的S100阳性细胞较少（P < 0.01），效应T细胞较少（P = 0.026）。对于PCNSL患者，背景中细胞毒性T细胞较少是一个不良预后因素（P = 0.004）。肿瘤内S100阳性细胞浸润与T细胞浸润及T细胞边缘模式呈正相关。
与非CNS DLBCL相比，PCNSL的基线抗肿瘤免疫反应较弱，这种反应可能在较差的预后中起作用。辅助性树突状细胞和T细胞免疫疗法可能会进一步提高PCNSL患者的治疗反应。
