Dolcetti Riccardo, Gloghini Annunziata, Caruso Arnaldo, Carbone Antonino
Cancer Bio-Immunotherapy Unit, Centro di Riferimento Oncologico-Istituto di ricovero e cura a carattere scientifico, National Cancer Institute, Aviano, Italy; University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, QLD, Australia;
Department of Diagnostic Pathology and Laboratory Medicine, Fondazione Istituto di ricovero e cura a carattere scientifico Istituto Nazionale dei Tumori, Milano, Italy;
Blood. 2016 Mar 17;127(11):1403-9. doi: 10.1182/blood-2015-11-681411. Epub 2016 Jan 14.
Despite the immune reconstitution promoted by combined antiretroviral therapy (cART), lymphomas still represent the most common type of cancer in HIV-infected individuals. Cofactors related to immunodeficiency such as oncogenic viruses, chronic antigenic stimulation, and cytokine overproduction are thought to be the main drivers of HIV lymphomagenesis, although the current scenario does not convincingly explain the still-high incidence of lymphomas and the occurrence of peculiar lymphoma histotypes in HIV-infected patients under cART. Recent findings are challenging the current view of a mainly indirect role of HIV in lymphoma development and support the possibility that HIV may directly contribute to lymphomagenesis. In fact, mechanisms other than immune suppression involve biologic effects mediated by HIV products that are secreted and accumulate in lymphoid tissues, mainly within lymph node germinal centers. Notably, HIV-infected patients with lymphomas, but not those not affected by these tumors, were recently shown to carry HIV p17 protein variants with enhanced B-cell clonogenic activity. HIV p17 protein variants were characterized by the presence of distinct insertions at the C-terminal region of the protein responsible for a structural destabilization and the acquisition of novel biologic properties. These data are changing the current paradigm assuming that HIV is only indirectly related to lymphomagenesis. Furthermore, these recent findings are consistent with a role of HIV as a critical microenvironmental factor promoting lymphoma development and pave the way for further studies that may lead to the design of more effective strategies for an early identification and improved control of lymphomas in the HIV setting.
尽管联合抗逆转录病毒疗法（cART）可促进免疫重建，但淋巴瘤仍是HIV感染者中最常见的癌症类型。与免疫缺陷相关的辅助因子，如致癌病毒、慢性抗原刺激和细胞因子过度产生，被认为是HIV淋巴瘤发生的主要驱动因素，尽管目前的情况并不能令人信服地解释HIV感染者在接受cART治疗时淋巴瘤的高发病率以及特殊淋巴瘤组织学类型的出现。最近的研究结果正在挑战目前认为HIV在淋巴瘤发展中主要起间接作用的观点，并支持HIV可能直接促进淋巴瘤发生的可能性。事实上，除了免疫抑制之外，其他机制还涉及HIV产物介导的生物学效应，这些产物在淋巴组织中分泌并积累，主要在淋巴结生发中心内。值得注意的是，最近发现患有淋巴瘤的HIV感染者携带具有增强B细胞克隆活性的HIV p17蛋白变体，而未受这些肿瘤影响的患者则没有。HIV p17蛋白变体的特征是在蛋白质的C末端区域存在独特的插入，这导致了结构不稳定并获得了新的生物学特性。这些数据正在改变目前认为HIV仅与淋巴瘤发生间接相关的范式。此外，这些最新发现与HIV作为促进淋巴瘤发展的关键微环境因素的作用相一致，并为进一步研究铺平了道路，这些研究可能会导致设计出更有效的策略，以便在HIV环境中早期识别和更好地控制淋巴瘤。
