Muris J J F, Meijer C J L M, Cillessen S A G M, Vos W, Kummer J A, Bladergroen B A, Bogman M J J T, MacKenzie M A, Jiwa N M, Siegenbeek van Heukelom L H, Ossenkoppele G J, Oudejans J J
Department of Clinical Pathology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
Leukemia. 2004 Mar;18(3):589-96. doi: 10.1038/sj.leu.2403240.
Clinical outcome in diffuse large B-cell lymphoma (DLBCL) remains unpredictable, despite the identification of clinical prognostic parameters. Here, we investigated in pretreatment biopsies of 70 patients with DLBCL whether numbers of activated cytotoxic T-lymphocytes (CTLs), as determined by the percentage of CD3-positive lymphocytes with granzyme B (GrB) expression, have similar prognostic value as found earlier in Hodgkin's lymphoma and anaplastic large-cell lymphoma and whether loss of major histocompatibility complex (MHC)-I molecules or expression of the GrB antagonist protease inhibitor 9 (PI9) may explain immune escape from CTL-mediated cell death. Independent of the International Prognostic Index (IPI), the presence of >/=15% activated CTLs was strongly associated with failure to reach complete remission, with a poor progression-free and overall survival time. Downregulation of MHC-I light- and/or heavy-chain expression was found in 41% of interpretable cases and in 19 of 56 interpretable cases PI9 expression was detected. We conclude that a high percentage of activated CTLs is a strong, IPI independent, indicator for an unfavorable clinical outcome in patients with primary nodal DLBCL. Although in part of DLBCL expression of PI9 and loss of MHC-I expression was found, providing a possible immune-escape mechanism in these cases, no correlation with clinical outcome was found.
尽管已经确定了临床预后参数，但弥漫性大B细胞淋巴瘤（DLBCL）的临床结局仍然不可预测。在此，我们对70例DLBCL患者的预处理活检样本进行研究，以确定通过表达颗粒酶B（GrB）的CD3阳性淋巴细胞百分比所确定的活化细胞毒性T淋巴细胞（CTL）数量是否具有与先前在霍奇金淋巴瘤和间变性大细胞淋巴瘤中发现的相似的预后价值，以及主要组织相容性复合体（MHC）-I分子的缺失或GrB拮抗剂蛋白酶抑制剂9（PI9）的表达是否可以解释免疫逃逸导致的CTL介导的细胞死亡。独立于国际预后指数（IPI），活化CTLs≥15%与未达到完全缓解、无进展生存期和总生存期较差密切相关。在41%的可解释病例中发现了MHC-I轻链和/或重链表达下调，在56例可解释病例中的19例中检测到了PI9表达。我们得出结论，活化CTLs的高百分比是原发性淋巴结DLBCL患者不良临床结局的一个强有力的、独立于IPI的指标。虽然在部分DLBCL中发现了PI9表达和MHC-I表达缺失，为这些病例提供了一种可能的免疫逃逸机制，但未发现与临床结局相关。
