Bosch Príncep Ramón, Lejeune Marylène, Salvadó Usach Maria Teresa, Jaén Martínez Joaquín, Pons Ferré Lluis E, Alvaro Naranjo Tomás
Department of Pathology, Hospital de Tortosa Verge de la Cinta, C/Esplanetes No. 44-56, 43500 Tortosa, Spain.
Ann Hematol. 2005 Oct;84(10):661-6. doi: 10.1007/s00277-005-1051-3. Epub 2005 May 5.
This study aimed to assess the differences in the cellular composition of the inflammatory reactive background around tumoral cells of classical Hodgkin's lymphomas (cHL) inside and outside the HIV settings. This retrospective study evaluates the infiltrating T lymphocytes (CD4 and CD8), natural killer cells (CD57+ cells), and more especially cytotoxic cells [granzyme B (GrB) and TIA-1+ cells] in the background of 99 EBV+ cHL. Sections from paraffin-embedded tumor samples from nine HIV-infected cHL patients were immunostained, using standard immunohistochemical protocols and were compared to a control group of 90 HIV-noninfected cHL patients. Our clinical and histological data indicate that HIV-infected cHL patients present a higher frequency of mixed cellularity (MC) histological subtypes, more advanced disease stages, a poor response to treatment, and a poor overall survival compared to control patients. In controls, CD4/CD8 and GrB/TIA-1 ratios were determined as 2:1 and 1:2, respectively. The inflammatory infiltrate of HIV-infected patients had a significant reduction of CD4+ T lymphocytes (CD4/CD8 ratio 1:23), a decrease in infiltrating GrB+ cells (activated cytotoxic cells) and an increase in infiltrating TIA+ T cells (mainly nonactivated cytotoxic cells) in these patients (GrB/TIA-1 ratio 1:12). In conclusion, this study highlights an important intratumoral loss of CD4+ T cells (striking inversion in the CD4/CD8 ratio) and a decrease in intratumoral activated cytotoxic T lymphocytes in HIV-associated cHL patients. Further studies are required to confirm these results and to determine the role of these findings on the antitumoral immune response observed in HIV-associated cHL.
本研究旨在评估在感染HIV和未感染HIV的情况下，经典型霍奇金淋巴瘤（cHL）肿瘤细胞周围炎症反应背景的细胞组成差异。这项回顾性研究评估了99例EBV阳性cHL患者背景中的浸润性T淋巴细胞（CD4和CD8）、自然杀伤细胞（CD57+细胞），尤其是细胞毒性细胞[颗粒酶B（GrB）和TIA-1+细胞]。对9例HIV感染的cHL患者石蜡包埋肿瘤样本的切片进行免疫染色，采用标准免疫组织化学方法，并与90例未感染HIV的cHL患者对照组进行比较。我们的临床和组织学数据表明，与对照患者相比，HIV感染的cHL患者具有更高频率的混合细胞性（MC）组织学亚型、更晚期的疾病阶段、对治疗反应较差以及总生存率较低。在对照组中，CD4/CD8和GrB/TIA-1比率分别确定为2:1和1:2。HIV感染患者的炎症浸润中，CD4+ T淋巴细胞显著减少（CD4/CD8比率为1:23），浸润的GrB+细胞（活化的细胞毒性细胞）减少，浸润的TIA+ T细胞（主要是非活化的细胞毒性细胞）增加（GrB/TIA-1比率为1:12）。总之，本研究强调了HIV相关cHL患者肿瘤内CD4+ T细胞的重要缺失（CD4/CD8比率显著倒置）以及肿瘤内活化细胞毒性T淋巴细胞的减少。需要进一步研究来证实这些结果，并确定这些发现对HIV相关cHL中观察到的抗肿瘤免疫反应的作用。
