Alonso-Álvarez Sara, Vidriales Maria Belén, Caballero Maria Dolores, Blanco Oscar, Puig Noemí, Martin Alejandro, Peñarrubia Maria Jesús, Zato Esther, Galende Josefina, Bárez Abelardo, Alcoceba Miguel, Orfão Alberto, González Marcos, García-Sanz Ramón
a IBMCC (USAL-CSIC) , Hospital Universitario de Salamanca-IBSAL , Salamanca , Spain.
b Hospital Clínico Universitario de Valladolid , Valladolid , Spain.
Leuk Lymphoma. 2017 May;58(5):1144-1152. doi: 10.1080/10428194.2016.1239263. Epub 2016 Oct 12.
Prognostic factors in Hodgkin lymphoma (HL) still fail to accurately identify high-risk patients. Tumor microenvironment in HL is a current focus of research for risk definition but few studies have focused on infiltrating lymphocytes. Here, we analyzed the number of tumor infiltrating lymphocytes by flow cytometry in diagnostic biopsies from 96 HL homogeneously treated patients with ABVD with or without radiotherapy. Most lymph node cells were lymphocytes (90 ± 17), with a median T/B/NK distribution of 74%/26%/0.7%, and CD4 T-cell predominance. The amount of CD19 B cells, and NK cells did not show association with disease features. However, high numbers of CD8 and CD4 cells were associated with better and poorer outcomes, respectively. Patients with ≥15% cytotoxic CD8 cells among the total cell population had a longer 10-year freedom from treatment failure (FFTF) (93% vs. 73%, p=.04). In turn, cases with ≥75% of CD4 infiltrating cells showed a significantly decreased FFTF (73% vs. 96%, p=.021). Consequently, CD4/CD8 ratio ≥5 associated with a poorer 10-year FFTF (69.5% vs. 94%, p=.02). This deleterious effect was particularly prominent in advanced disease (n = 58, p=.01). In multivariate analysis, a CD4/CD8 ratio ≥5 was the only independent variable to predict for treatment failure (HR = 4.5, 95% confidence interval, 1.2-16.8). In conclusion, our study shows that high CD4 and low CD8 T-cells infiltrates of tumor specimens associate with poor prognosis in HL patients, and CD4/CD8 ratio might be potentially useful for tailoring therapy.
霍奇金淋巴瘤（HL）的预后因素仍无法准确识别高危患者。HL中的肿瘤微环境是目前风险定义研究的重点，但很少有研究关注浸润淋巴细胞。在此，我们通过流式细胞术分析了96例接受ABVD方案治疗（有或无放疗）的HL患者诊断性活检标本中的肿瘤浸润淋巴细胞数量。大多数淋巴结细胞为淋巴细胞（90±17），T/B/NK细胞的中位分布为74%/26%/0.7%，且以CD4 T细胞为主。CD19 B细胞和NK细胞的数量与疾病特征无关。然而，CD8细胞数量多与较好的预后相关，而CD4细胞数量多则与较差的预后相关。总细胞群中细胞毒性CD8细胞≥15%的患者10年无治疗失败生存期（FFTF）更长（93%对73%，p = 0.04）。反过来，CD4浸润细胞≥75%的病例FFTF显著降低（73%对96%，p = 0.021）。因此，CD4/CD8比值≥5与10年FFTF较差相关（69.5%对94%，p = 0.02）。这种有害影响在晚期疾病中尤为突出（n = 58，p = 0.01）。在多变量分析中，CD4/CD8比值≥5是预测治疗失败的唯一独立变量（风险比=4.5，95%置信区间，1.2 - 16.8）。总之，我们的研究表明，肿瘤标本中CD4 T细胞浸润高而CD8 T细胞浸润低与HL患者预后不良相关，且CD4/CD8比值可能对调整治疗方案有潜在帮助。
