Experimental and Clinical Oncology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Eur J Haematol. 2018 Jan;100(1):88-97. doi: 10.1111/ejh.12987. Epub 2017 Nov 14.
The classical Hodgkin lymphoma (cHL) tumor microenvironment shows an ongoing inflammatory response consisting of varying degrees of infiltrating eosinophils, mast cells, macrophages, regulatory T lymphocytes (Tregs), and activated lymphocytes surrounding the malignant cells. Herein, different immune signatures are characterized and correlated with treatment outcome.
Tumor-infiltrating leukocytes were phenotyped in biopsies from 459 patients with cHL. Time to progression (TTP) (primary progression, relapse, or death from cHL) and overall survival were analyzed using Cox proportional hazards regression.
The leukocyte infiltration in the microenvironment was highly diverse between patients and was categorized in 4 immune signatures (active, anergic, innate, or mixed). A high proportion of Tregs (anergic) resulted in shorter TTP (median 12.9-year follow-up) in age-adjusted analyses (hazard ratio = 1.82; 95% confidence interval 1.05-3-15). Epstein-Barr virus (EBV)-positive cases had higher proportions of macrophages and activated lymphocytes than EBV negative, but neither of those leukocytes predicted prognosis.
Abundant Tregs (anergic signature) indicate a shorter TTP, particularly in younger patients. This is probably due to a reduced ability of the immune system to attack the tumor cells. Our data warrant further investigation if these suggested immune signatures could predict outcome of immunotherapy such as immune checkpoint inhibitors.
经典霍奇金淋巴瘤（cHL）肿瘤微环境表现为持续的炎症反应，其中包括不同程度浸润的嗜酸性粒细胞、肥大细胞、巨噬细胞、调节性 T 淋巴细胞（Tregs）和围绕恶性细胞的活化淋巴细胞。在此，我们对不同的免疫特征进行了描述，并与治疗结果相关联。
对 459 例 cHL 患者的活检标本中的肿瘤浸润白细胞进行了表型分析。使用 Cox 比例风险回归分析无进展生存期（TTP）（原发性进展、复发或 cHL 死亡）和总生存期。
患者之间的微环境中白细胞浸润高度多样化，并分为 4 种免疫特征（活跃、无反应、先天或混合）。高比例的 Tregs（无反应）导致 TTP 缩短（中位随访 12.9 年），在年龄调整分析中（风险比=1.82；95%置信区间 1.05-3-15）。EBV 阳性病例的巨噬细胞和活化淋巴细胞比例高于 EBV 阴性病例，但这两种白细胞均不能预测预后。
大量的 Tregs（无反应特征）预示着 TTP 更短，尤其是在年轻患者中。这可能是由于免疫系统攻击肿瘤细胞的能力降低所致。如果这些免疫特征可以预测免疫检查点抑制剂等免疫治疗的预后，我们的数据需要进一步研究。
