Genetic Modulation of Effector Cells to Enhance GVL Effects

Viral respiratory infections are recognized risk factors for the loss of control of allergic asthma and the induction of exacerbations, both in adults and children. Severe asthma is more susceptible to virus-induced asthma exacerbations, especially in the presence of high IgE levels. In the course of immune responses to viruses, an initial activation of innate immunity typically occurs and the production of type I and III interferons is essential in the control of viral spread. However, the Th2 inflammatory environment still appears to be protective against viral infections in general and in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections as well. As for now, literature data, although extremely limited and preliminary, show that severe asthma patients treated with biologics don’t have an increased risk of SARS-CoV-2 infection or progression to severe forms compared to the non-asthmatic population. Omalizumab, an anti-IgE monoclonal antibody, exerts a profound cellular effect, which can stabilize the effector cells, and is becoming much more efficient from the point of view of innate immunity in contrasting respiratory viral infections. In addition to the antiviral effect, clinical efficacy and safety of this biological allow a great improvement in the management of asthma.

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Phenotypical and Functional Characteristics of Human Regulatory T Cells during Ex Vivo Maturation from CD4+ T Lymphocytes

Applied Sciences ◽

10.3390/app11135776 ◽

2021 ◽

Vol 11 (13) ◽

pp. 5776

Author(s):

Varvara G. Blinova ◽

Natalia S. Novachly ◽

Sofya N. Gippius ◽

Abdullah Hilal ◽

Yulia A. Gladilina ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Ex Vivo ◽

Pcr Analysis ◽

Mrna Levels ◽

Rt Pcr ◽

Inflammatory Reactions ◽

Effector Cells ◽

Cycle Regulation ◽

Further Development

Regulatory T cells (Tregs) participate in the negative regulation of inflammatory reactions by suppressing effector cells. In a number of autoimmune disorders, the suppressive function and/or the number of Tregs is compromised. The lack of active functioning Tregs can be restored with adoptive transfer of expanded ex vivo autologous Tregs. In our study, we traced the differentiation and maturation of Tregs CD4+CD25+FoxP3+CD127low over 7 days of cultivation from initial CD4+ T cells under ex vivo conditions. The resulting ex vivo expanded cell population (eTregs) demonstrated the immune profile of Tregs with an increased capacity to suppress the proliferation of target effector cells. The expression of the FoxP3 gene was upregulated within the time of expansion and was associated with gradual demethylation in the promotor region of the T cell-specific demethylation region. Real-time RT-PCR analysis revealed changes in the expression profile of genes involved in cell cycle regulation. In addition to FOXP3, the cells displayed elevated mRNA levels of Ikaros zinc finger transcription factors and the main telomerase catalytic subunit hTERT. Alternative splicing of FoxP3, hTERT and IKZF family members was demonstrated to be involved in eTreg maturation. Our data indicate that expanded ex vivo eTregs develop a Treg-specific phenotype and functional suppressive activity. We suggest that eTregs are not just expanded but transformed cells with enhanced capacities of immune suppression. Our findings may influence further development of cell immunosuppressive therapy based on regulatory T cells.

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Immunosurveillance of Cancer and Viral Infections with Regard to Alterations of Human NK Cells Originating from Lifestyle and Aging

Biomedicines ◽

10.3390/biomedicines9050557 ◽

2021 ◽

Vol 9 (5) ◽

pp. 557

Author(s):

Xuewen Deng ◽

Hiroshi Terunuma ◽

Mie Nieda

Keyword(s):

Nk Cells ◽

Viral Infections ◽

Nk Cell ◽

Healthy Lifestyle ◽

Cell Activity ◽

Nk Cell Activity ◽

Effector Cells ◽

Cell Dysfunction ◽

Forest Bathing ◽

Infected Cells

Natural killer (NK) cells are cytotoxic immune cells with an innate capacity for eliminating cancer cells and virus- infected cells. NK cells are critical effector cells in the immunosurveillance of cancer and viral infections. Patients with low NK cell activity or NK cell deficiencies are predisposed to increased risks of cancer and severe viral infections. However, functional alterations of human NK cells are associated with lifestyles and aging. Personal lifestyles, such as cigarette smoking, alcohol consumption, stress, obesity, and aging are correlated with NK cell dysfunction, whereas adequate sleep, moderate exercise, forest bathing, and listening to music are associated with functional healthy NK cells. Therefore, adherence to a healthy lifestyle is essential and will be favorable for immunosurveillance of cancer and viral infections with healthy NK cells.

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Immune Monitoring during Therapy Reveals Activitory and Regulatory Immune Responses in High-Risk Neuroblastoma

Cancers ◽

10.3390/cancers13092096 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2096

Author(s):

Celina L. Szanto ◽

Annelisa M. Cornel ◽

Sara M. Tamminga ◽

Eveline M. Delemarre ◽

Coco C. H. de Koning ◽

...

Keyword(s):

T Cells ◽

High Risk ◽

Nk Cells ◽

Immune Cell ◽

High Dose Chemotherapy ◽

Immune Monitoring ◽

High Dose ◽

Effector Cells ◽

Gm Csf ◽

Immune Cell Subsets

Despite intensive treatment, including consolidation immunotherapy (IT), prognosis of high-risk neuroblastoma (HR-NBL) is poor. Immune status of patients over the course of treatment, and thus immunological features potentially explaining therapy efficacy, are largely unknown. In this study, the dynamics of immune cell subsets and their function were explored in 25 HR-NBL patients at diagnosis, during induction chemotherapy, before high-dose chemotherapy, and during IT. The dynamics of immune cells varied largely between patients. IL-2- and GM-CSF-containing IT cycles resulted in significant expansion of effector cells (NK-cells in IL-2 cycles, neutrophils and monocytes in GM-CSF cycles). Nonetheless, the cytotoxic phenotype of NK-cells was majorly disturbed at the start of IT, and both IL-2 and GM-CSF IT cycles induced preferential expansion of suppressive regulatory T-cells. Interestingly, proliferative capacity of purified patient T-cells was impaired at diagnosis as well as during therapy. This study indicates the presence of both immune-enhancing as well as regulatory responses in HR-NBL patients during (immuno)therapy. Especially the double-edged effects observed in IL-2-containing IT cycles are interesting, as this potentially explains the absence of clinical benefit of IL-2 addition to IT cycles. This suggests that there is a need to combine anti-GD2 with more specific immune-enhancing strategies to improve IT outcome in HR-NBL.

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