Biology subjects

Zenarruzabeitia, O.

Publications and source records attributed to Zenarruzabeitia, O..

4 recordsLinked to original sources

bioRxiv2024

Activated NK cells with a predominance of inhibitory receptors and a decidual-like phenotype expand after autologous HSCT in children with tumors.

Early immune reconstitution after autologous hematopoietic stem cell transplantation (autoHSCT) is associated with a better outcome in a variety of cancers. NK cells constitute the first lymphocyte subset to recover in the blood after autoHSCT. We have in-depth characterized them in pediatric patients with different tumors and found that, immediately after autoHSCT, NK cells transiently acquired a decidual-like phenotype, were more immature and activated, and exhibited an increased expression of inhibitory receptors, while activating receptors levels were diminished. This activated and decidual-like phenotype was characterized by increased CD56, CD9, CD49a, CD151, CD38, HLA-DR and CD55 expression. We also determined plasma levels of several cytokines and found that their concentrations were associated with the observed changes in NK cells phenotype. In vitro experiments, including flow cytometry and single-cell RNA sequencing (scRNA-seq), recapitulated the changes observed in NK cells early after autoHSCT. Specifically, results revealed that the combination of IL-15 and TGF-{beta} induced, at least partially, this distinctive phenotype on NK cells after autoHSCT. Finally, we have observed a positive correlation between relapse and the percentage of CD56dim NK cells shortly after autoHSCT in our cohort of pediatric patients. Altogether, our work is of relevance to understand the physiopathology of NK cells during the immune system reconstitution after autoHSCT in children and potentially help in the management of these patients.

immunology↗

bioRxiv2020

T cell activation, highly armed cytotoxic cells and a sharp shift in monocytes CD300 receptors expression is characteristic of patients with severe COVID-19

COVID-19 manifests with a wide diversity of clinical phenotypes characterized by dysfunctional and exaggerated host immune responses. Many results have been described on the status of the immune system of patients infected with SARS-CoV-2, but there are still aspects that have not been fully characterized. In this study, we have analyzed a cohort of patients with mild, moderate and severe disease. We performed flow cytometric studies and correlated the data with the clinical features and clinical laboratory values of patients. Both conventional and unsupervised data analyses concluded that patients with severe disease are characterized, among others, by a higher state of activation in all T cell subsets, higher expression of perforin and granzyme B in cytotoxic cells, expansion of adaptive NK cells and the accumulation of activated and immature dysfunctional monocytes which are identified by a low expression of HLA-DR and an intriguing abrupt change in the expression pattern of CD300 receptors. More importantly, correlation analysis showed a strong association between the alterations in the immune cells and the clinical signs of severity. These results indicate that patients with severe COVID-19 have a broad perturbation of their immune system, and they will help to understand the immunopathogenesis of severe COVID-19 as well as could be of special value for physicians to decide which specific therapeutic options are most effective for their patients.

immunology↗

bioRxiv2020

Human cytokine-induced memory-like NK cells preserve increased glycolysis but the glycolytic-dependence of their effector functions differ between stimuli

Natural Killer (NK) cells acquire memory-like properties following a brief stimulation with IL-12, IL-15 and IL-18. These IL-12/15/18-stimulated NK cells, also known as cytokine-induced memory-like (CIML) NK cells, have been revealed as a powerful tool in cancer immunotherapy due to their persistence in the host and their increased effector functions. Several studies have shown that NK cells modulate their metabolism in response to cytokine-stimulation and other stimuli, suggesting that there is a link between metabolism and cellular functions. In this paper, we have analyzed metabolic changes associated to IL-12/15/18-stimulation and the relevance of glycolytic pathway for NK cell effector functions. We have found that CIML NK cells are able to retain increased glycolytic machinery seven days after cytokine withdrawal. Furthermore, we found that glycolytic inhibition with 2-DG is stimuli-dependent and that differently affects to distinct effector functions. These findings may have implications in the design of NK cell-based cancer immunotherapies.

immunology↗

bioRxiv2020

A NKp80-based identification strategy reveals that CD56neg NK cells are not completely dysfunctional in health and disease.

Natural killer (NK) cells are usually identified by the absence of other lineage markers, due to the lack of a cell surface specific marker. CD56neg NK cells, classically identified as CD56negCD16+ are known to be expanded in some pathological conditions. However, studies on CD56neg NK cells had revealed different results regarding the phenotype and functionality of these cells. This could be due to, among others, the unstable expression of CD16, which hinders CD56neg NK cells identification. Hence, we aim to determine an alternative surface marker to CD16 to better identify CD56neg NK cells. Using multiparametric flow cytometry, we have found that NKp80 is a good alternative to CD16 not only in healthy donors but also in HIV-1 infected subjects and multiple myeloma patients. Furthermore, we found differences between the functionality of CD56negNKp80+ and CD56negCD16+ NK cells both in healthy donors and patients, suggesting that the effector functions of CD56neg NK cells are not as diminished as previously thought. We proposed NKp80 as a noteworthy marker to identify and accurately re-characterize human CD56neg NK cells.

immunology↗