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。