Bortezomib induces HSV-1 lethality in mice with neutrophil deficiency.

Bortezomib induces HSV-1 lethality in mice with neutrophil deficiency. J Leukoc Biol. 2019 Nov 15;: Authors: Yao HW, Wang LC, Tsai HY, Fang YH, Zheng C, Chen SH, Hsu SM Abstract Bortezomib suppressing NF-κB activity is an effective therapy for patients with myeloma or lymphoma. However, this drug can cause adverse effects, neutropenia, and recurrent infections of herpes viruses. Among herpes viruses, HSV-1 can reactivate to induce mortality. The important issues regarding how bortezomib diminishes neutrophils, whether bortezomib can induce HSV-1 reactivation, and how bortezomib exacerbates HSV-1 infection, need investigation. Using the murine model, we found that bortezomib induced HSV-1 reactivation. Bortezomib diminished neutrophil numbers in organs of uninfected and HSV-1-infected mice and turned a nonlethal infection to lethal with elevated tissue viral loads. In vitro results showed that bortezomib and HSV-1 collaborated to enhance the death and apoptosis of mouse neutrophils. The leukocyte deficiency induced by chemotherapies is generally believed to be the cause for aggravating virus infections. Here we show the potential of pathogen to exacerbate chemotherapy-induced leukocyte deficiency. PMID: 31729784 [PubMed - as supplied by publisher]
Source: Journal of Leukocyte Biology - Category: Hematology Authors: Tags: J Leukoc Biol Source Type: research

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Oncolytic viruses (OV) are genetically modified viruses that specifically infect and lyse tumor cells. So far, OV monotherapy shows only limited benefit in clinical practice. However, it holds great potential in combinatorial treatment approaches. Natural killer cells recognize and kill infected, stressed or malignant cells without prior antigen exposure. Patients who lack NK cells are highly susceptible to severe and recurrent herpesvirus (HSV) infections. Thus, the combination of HSV based OVs (HSV-OV) and NK cells has a strong rationale.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research
Conclusion and Future Perspectives This review illustrates our current knowledge of USP7, including its source and characterization, structure, binding partners and substrates in various biological processes. Besides, how USP7 regulates various aspects of a cell under both normal and pathological states are elaborated in detail. As the processes of ubiquitination and deubiquitination are extremely dynamic and context-specific, a series of studies have linked USP7 to different cancers. The biology, particularly the immune oncology mechanisms, reveal that USP7 inhibitors would be useful drugs, thus it is vital to develop hi...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusions Epidemiological studies have repeatedly helped identify definitive triggers for several diseases. As highlighted in this perspective report, previous studies strongly argue for the interplay between intrinsic factors and putative preventable extrinsic triggers/promoters for CTCL. Given the evidence of geographical regional clustering of CTCL patients, CTCL occurrence in unrelated family members and recent evidence implicating S. aureus in the pathogenesis/progression of CTCL, more research is needed to decipher the precise mechanism by which specific environmental exposures may be driving the pathogenesis of t...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions In conclusion, articles in this Research Topic made a very significant contribution to our understanding of the role played by environmental factors, dysbiotic conditions, and infections in triggering diseases. Since this is a rapidly expanding area of research, many other factors contributing to the onset of these diseases are not covered here. We are confident, however, that further studies will expand the list as well as bring a better understanding of mechanisms involved in the onset of autoimmune and autoinflammatory diseases. Author Contributions All authors listed have made a substantial, direct and i...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Discussion In this section, we discuss the mechanisms responsible for lymphomagenesis in the various inborn errors of immunity and provide an overview of the treatment. Defects in Immune Responses That Predispose to Lymphomagenesis in PIDDs The complex immune mechanisms and their interplay that predisposes to neoplastic transformation of B or T cells and development of lymphomas in PIDD patients has not been fully elucidated. However, it is expected that the etiology in most cases is multifactorial and related to a dynamic regulation of immune response and environmental triggers (Figure 3). An underlying intrinsic susce...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
ConclusionDespite the small sample size, our data show that consolidative auto-HCT is safe and could be considered for eligible PEL patients after induction chemotherapy. However, a high relapse rate is concerning and warrants incorporation of new strategies to mitigate post-transplantation relapse.
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
Publication date: Available online 19 December 2018Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Yamila Goenaga Vázquez, Fernando Cabanillas, Joel Rivera Concepción, Olga L. Díaz MirandaAbstractHerpes Zoster (HZ) is associated with significant mortality and morbidity in patients with lymphoma. This is a retrospective cohort study conducted to determine the incidence and risk factors for developing HZ in this cohort. Receiving highly immunosuppressive chemotherapy is an independent risk factor for developing HZ. Prophylaxis against HZ should be considered for this population in order to minim...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
Conclusions Our patient’s high CD4+ cell count, lack of pre-existing AIDS diagnosis and excellent response to chemotherapy highlights that HHV-8-LBL may have a distinct clinical picture and possibly a better response to chemotherapy than classic PEL. HHV-8-LBL should be included in the differential diagnosis of HIV patients with solid lesions. It is essential that patients’ CDC HIV clinical status and HIV viral load at time of diagnosis of PEL and HHV-8-LBL be reported and that clinical results include longer-term follow-up. Only then can a more complete clinical picture of this little appreciated and understoo...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
Conclusion: HZ is associated with modestly increased risk of a few cancers, particularly hematologic malignancies. Associations were strongest at short latency intervals for many cancers, and for regional/distant stages among solid cancers, perhaps reflecting reverse causality. Impact: Age-related immune decline does not play a major role in cancer development in older people, but it may be important for some lymphomas. Cancer Epidemiol Biomarkers Prev; 25(1); 28–35. ©2015 AACR.
Source: Cancer Epidemiology Biomarkers and Prevention - Category: Cancer & Oncology Authors: Tags: Cancer Surveillance Research Source Type: research
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