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(A) Clinical findings. Exposed root surfaces of the teeth 33–43 due to severe gingivitis and periodontitis in an age of 24 years. (B) Orthopantomogram. General alveolar bone loss caused by severe chronic periodontitis. The wisdom teeth 18 and 38 are partially erupted and the mandibular anterior teeth are stabilized by a retainer.
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Most of the few patients with homozygous CD70 deficiency described to date suffered from EBV-related malignancies in early childhood. We present a woman with CD70 deficiency diagnosed in adulthood. She presented in childhood with recurrent airway infections due to encapsulated bacteria, herpes zoster and a fulminant EBV infection followed by chroni...
Citations
... On possible reason for immune suppression is host gene mutation, with CD27 or CD70 deficiency being common (Guan et al., 2021). In CAEBV patients, the interaction between CD27 and CD70 is crucial as it induces protective EBV-specific T cell immunity and immune surveillance of infected-B cells, which is due to the expansion of EBV-specific T cells (Izawa et al., 2017;Kruger et al., 2020). CD27 is especially vital in the expansion of lytic EBV antigen-specific CD8 + T cells, and blocking the CD27-CD70 pathway compromises EBV-specific immune control . ...
Epstein-Barr virus (EBV) infection is extremely common worldwide, with approximately 90% of adults testing positive for EBV antibodies. Human are susceptible to EBV infection, and primary EBV infection typically occurs early in life. EBV infection can cause infectious mononucleosis (IM) as well as some severe non-neoplastic diseases, such as chronic active EBV infection (CAEBV) and EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), which can have a heavy disease burden. After primary EBV infection, individuals develop robust EBV-specific T cell immune responses, with EBV-specific CD8+ and part of CD4+ T cells functioning as cytotoxic T cells, defending against virus. Different proteins expressed during EBV's lytic replication and latent proliferation can cause varying degrees of cellular immune responses. Strong T cell immunity plays a key role in controlling infection by decreasing viral load and eliminating infected cells. However, the virus persists as latent infection in EBV healthy carriers even with robust T cell immune response. When reactivated, it undergoes lytic replication and then transmits virions to a new host. Currently, the relationship between the pathogenesis of lymphoproliferative diseases and the adaptive immune system is still not fully clarified and needs to be explored in the future. Investigating the T cell immune responses evoked by EBV and utilizing this knowledge to design promising prophylactic vaccines are urgent issues for future research due to the importance of T cell immunity.
... Therefore, direct targeting of CD70 + tumor cells might further inhibit Treg accumulation and activation in NPC. However, recent studies have suggested that CD70 deficiency in EBV-infected patients might exacerbate chronic EBV infection and predispose them to lymphoma and immune disorders (69,70). As CD70 is also expressed on CD8 + effector T cells and activated B cells, lack of functional CD70 might hinder T and B cell-mediated immunity to combat EBV infection and further promote tumor progression. ...
The evolution of the tumor microenvironment (TME) is a cancer-dependent and dynamic process. The TME is often a complex ecosystem with immunosuppressive and tumor-promoting functions. Conventional chemotherapy and radiotherapy, primarily focus on inducing tumor apoptosis and hijacking tumor growth, whereas the tumor-protective microenvironment cannot be altered or destructed. Thus, tumor cells can quickly escape from extraneous attack and develop therapeutic resistance, eventually leading to treatment failure. As an Epstein Barr virus (EBV)-associated malignancy, nasopharyngeal carcinoma (NPC) is frequently infiltrated with varied stromal cells, making its microenvironment a highly heterogeneous and suppressive harbor protecting tumor cells from drug penetration, immune attack, and facilitating tumor development. In the last decade, targeted therapy and immunotherapy have emerged as promising options to treat advanced, metastatic, recurrent, and resistant NPC, but lack of understanding of the TME had hindered the therapeutic development and optimization. Single-cell sequencing of NPC-infiltrating cells has recently deciphered stromal composition and functional dynamics in the TME and non-malignant counterpart. In this review, we aim to depict the stromal landscape of NPC in detail based on recent advances, and propose various microenvironment-based approaches for precision therapy.
Biallelic mutations in the genes encoding CD27 or its ligand CD70 underlie inborn errors of immunity characterized predominantly by EBV-associated immune dysregulation, such as chronic viremia, severe infectious mononucleosis, hemophagocytic lymphohistiocytosis (HLH), lymphoproliferation and malignancy. A comprehensive understanding of the natural history, immune characteristics and transplant outcomes has remained elusive. Here, in a multi-institutional global collaboration, we collected clinical information of 49 patients from 29 families (CD27 n=33, CD70 n=16), including 24 previously unreported individuals and identified a total of 16 distinct mutations in CD27, and 8 in CD70, respectively. The majority (90%) of patients were EBV+ at diagnosis, but only ~30% presented with infectious mononucleosis. Lymphoproliferation and lymphoma were the main clinical manifestations (70% and 43%, respectively), and 9 of the CD27-deficient patients developed HLH. Twenty-one (43%) patients developed autoinflammatory features including uveitis, arthritis and periodic fever. Detailed immunological characterization revealed aberrant generation of memory B and T cells, including a paucity of EBV-specific T cells, and impaired effector function of CD8+ T cells, thereby providing mechanistic insight into cellular defects underpinning the clinical features of disrupted CD27/CD70 signaling. Nineteen patients underwent allogeneic hematopoietic stem cell transplantation (HSCT) prior to adulthood predominantly because of lymphoma, with 95% survival without disease recurrence. Our data highlight the marked predisposition to lymphoma of both CD27- and CD70-deficient patients. The excellent outcome after HSCT supports the timely implementation of this treatment modality particularly in patients presenting with malignant transformation to lymphoma.
