Global Clinical Assay Group, Pfizer, Inc, San Diego, California 92121, USA.
Cytometry B Clin Cytom. 2012 Mar;82(2):112-9. doi: 10.1002/cyto.b.20631. Epub 2011 Nov 10.
CD80 is a member of the B7 family of immune coregulatory proteins that mediate both immune activation and suppression. CD80 in particular has recently been shown to play an important role in supporting immune suppression through interactions with B7-H1. CD80 has been identified as a therapeutic target in non-Hodgkin lymphoma (NHL) based on limited immunohistochemical studies of CD80 expression. Clinical studies have shown that the anti-CD80 antibody galiximab is safe and clinically efficacious in follicular NHL. However, the mechanisms through which targeting CD80 inhibits tumor progression remain poorly understood.
To further define the potential of CD80 as a therapeutic target in NHL, CD80 expression was evaluated by multicolor flow cytometric analysis of primary lymphoma cell suspensions generated from 241 diagnostic biopsies of patients with NHL.
CD80 was expressed on malignant B cells in essentially all cases of follicular lymphoma (97%; n = 115), the majority of cases of diffuse large B-cell lymphoma (90%; n = 69), marginal zone lymphoma (91%; n = 22), mantle cell lymphoma (75%; n = 12), and in about half of small lymphocytic lymphoma cases (43%; n = 23). CD80 was also present on tumor-infiltrating T lymphocytes in nearly all cases. Additionally, CD80 was expressed by non-B, non-T cells in 68 and 44% of cases of follicular and diffuse large B-cell NHL, respectively.
CD80 is expressed on both malignant cells and the nonmalignant cells in NHL. Therapeutic targeting of CD80 will therefore modulate the complex intercellular interactions that define the tumor microenvironment in NHL.
CD80 是 B7 家族免疫协同调节蛋白的成员，可介导免疫激活和抑制。最近的研究表明，CD80 通过与 B7-H1 的相互作用在支持免疫抑制方面发挥重要作用。基于对 CD80 表达的有限免疫组化研究，CD80 已被确定为非霍奇金淋巴瘤（NHL）的治疗靶点。临床研究表明，抗 CD80 抗体 galiximab 在滤泡性 NHL 中安全且具有临床疗效。然而，靶向 CD80 抑制肿瘤进展的机制仍知之甚少。
为了进一步确定 CD80 作为 NHL 治疗靶点的潜力，通过对 241 例 NHL 患者的诊断性活检产生的原发性淋巴瘤细胞悬浮液进行多色流式细胞术分析，评估 CD80 的表达。
CD80 在几乎所有滤泡性淋巴瘤病例（97%；n=115）、大多数弥漫性大 B 细胞淋巴瘤病例（90%；n=69）、边缘区淋巴瘤病例（91%；n=22）、套细胞淋巴瘤病例（75%；n=12）和大约一半小淋巴细胞淋巴瘤病例（43%；n=23）的恶性 B 细胞上表达。CD80 也存在于几乎所有病例的肿瘤浸润性 T 淋巴细胞上。此外，CD80 在分别有 68%和 44%的滤泡性和弥漫性大 B 细胞 NHL 病例的非 B、非 T 细胞上表达。
CD80 在 NHL 的恶性细胞和非恶性细胞上均有表达。因此，CD80 的治疗性靶向将调节定义 NHL 肿瘤微环境的复杂细胞间相互作用。
