Medeiros L J, Gelb A B, Wolfson K, Doggett R, McGregor B, Cox R S, Horning S J, Warnke R A
Department of Pathology, Rhode Island Hospital, Providence 02903.
Am J Pathol. 1993 Oct;143(4):1086-97.
The major histocompatibility complex (MHC) class I (HLA-A, B, C) and class II (HLA-DR) antigens are involved in cell-to-cell recognition and in regulating the immune response. Others have shown previously that MHC class I and class II antigens may be absent in a subset of malignant lymphomas, prompting the hypothesis that the absence of MHC antigen expression may be one of the mechanisms involved in the growth and dissemination of malignant lymphomas (by allowing a neoplasm to escape immune surveillance). To address this hypothesis, we analyzed MHC class I and class II (HLA-DR) antigen expression by diffuse large cell and large cell immunoblastic lymphomas in 88 and 117 patients, respectively, using frozen sections and the monoclonal antibodies W6/32 (HLA-A, B, C), anti-beta 2-microglobulin, and L203 (HLA-DR). Although there were no statistically significant clinical differences by MHC class II antigen expression, a small group of patients with MHC class I antigen-negative lymphomas were significantly younger (P = 0.03), less often had small neoplasms (P = 0.03), and were treated with doxorubicin-based chemotherapy more frequently (P = 0.04) than those with antigen-positive lymphomas. However, neither MHC class I nor class II antigen expression by the lymphomas consistently correlated with patient survival or freedom from relapse. This lack of correlation was true for all patients assessed, as well as for the subsets of patients with B-cell lymphomas, T-cell neoplasms, or those treated with doxorubicin-based chemotherapy. In accordance with previously published studies, stage, presence of B symptoms, and treatment with doxorubicin-based chemotherapy were of prognostic importance in univariate or multivariate analyses for survival or freedom from relapse. The findings may be considered evidence against the hypothesis that the absence of MHC class I or II antigen expression by malignant lymphomas plays a role in their tumorigenicity. However, we cannot completely exclude the possibility that the therapies used for this group of patients may have obscured any effect that MHC antigen expression exerts on prognosis.
主要组织相容性复合体(MHC)I类(HLA - A、B、C)和II类(HLA - DR)抗原参与细胞间识别并调节免疫反应。其他人先前已表明,MHC I类和II类抗原可能在一部分恶性淋巴瘤中缺失,这促使人们提出假说,即MHC抗原表达缺失可能是恶性淋巴瘤生长和扩散的机制之一(通过使肿瘤逃避免疫监视)。为验证这一假说,我们分别对88例弥漫性大细胞淋巴瘤患者和117例大细胞免疫母细胞淋巴瘤患者的MHC I类和II类(HLA - DR)抗原表达进行了分析,采用冰冻切片以及单克隆抗体W6/32(HLA - A、B、C)、抗β2 - 微球蛋白和L203(HLA - DR)。尽管MHC II类抗原表达在临床上无统计学显著差异,但一小群MHC I类抗原阴性淋巴瘤患者比抗原阳性淋巴瘤患者明显更年轻(P = 0.03),肿瘤较小的情况更少见(P = 0.03),且接受基于阿霉素的化疗更频繁(P = 0.04)。然而,淋巴瘤的MHC I类和II类抗原表达均与患者生存率或无复发生存期无一致的相关性。对于所有评估的患者,以及B细胞淋巴瘤、T细胞肿瘤患者亚组或接受基于阿霉素化疗的患者亚组,这种缺乏相关性都是成立的。与先前发表的研究一致,在生存或无复发生存期的单变量或多变量分析中,分期、B症状的存在以及基于阿霉素的化疗对预后具有重要意义。这些发现可被视为反对恶性淋巴瘤MHC I类或II类抗原表达缺失在其致瘤性中起作用这一假说的证据。然而,我们不能完全排除用于该组患者的治疗方法可能掩盖了MHC抗原表达对预后所产生的任何影响的可能性。