The role of interleukin-15 in the development and treatment of hematological malignancies

Sindaco, Paola Del; Pandey, Hritisha; Isabelle, Colleen; Chakravarti, Nitin; Brammer, Jonathan E.; Porcu, Pierluigi; Mishra, Anjali

doi:10.3389/fimmu.2023.1141208

Cited by 10 publications

(5 citation statements)

References 144 publications

(102 reference statements)

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“…In summary, these are novel findings that may have physiological relevance in settings where the plasma and tissue levels of IL-15 are increased. These settings include hematologic and solid tumors, autoimmune diseases, HIV infection, neurodegenerative disorders, and also exercise training in healthy subjects ( 48 – 53 ). In the latter situation, an inverse relationship between IL-15 and adipose tissue mass indexes was observed, suggesting that IL-15 has beneficial metabolic activities in obesity and type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

In vitro IL-15-activated human naïve CD8+ T cells down-modulate the CD8β chain and become CD8αα T cells

Esgalhado,

Reste-Ferreira,

Weinhold

et al. 2024

Front. Immunol.

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Antigen-driven human effector-memory CD8+ T cells expressing low levels of the CD8β chain have been previously described. However, little is known on a possible antigen-independent trigger. We have examined the impact that IL-15 has on the expression of CD8β on purified human naïve CD8+ T cells after CFSE labeling and culture with IL-15. As expected, IL-15 induced naïve CD8+ T cells to proliferate and differentiate. Remarkably, the process was associated with a cell-cycle dependent down-modulation of CD8β from the cell surface, leading to the generation of CD8αβlow and CD8αβ− (i.e., CD8αα) T cells. In contrast, expression of the CD8α chain remained steady or even increased. Neither IL-2 nor IL-7 reproduced the effect of IL-15. Determination of mRNA levels for CD8α and CD8β isoforms by qPCR revealed that IL-15 promoted a significant decrease in mRNA levels of the CD8β M-4 isoform, while levels of the M-1/M-2 isoforms and of CD8α increased. Noteworthy, CD8+ T cell blasts obtained after culture of CD8+ T cells with IL-15 showed a cell-cycle dependent increase in the level of the tyrosine kinase Lck, when compared to CD8+ T cells at day 0. This study has shown for the first time that IL-15 generates CD8αα+αβlow and CD8αα+αβ− T cells containing high levels of Lck, suggesting that they may be endowed with unique functional features.

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Section: Discussionmentioning

confidence: 99%

In vitro IL-15-activated human naïve CD8+ T cells down-modulate the CD8β chain and become CD8αα T cells

Esgalhado,

Reste-Ferreira,

Weinhold

et al. 2024

Front. Immunol.

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“…These results were consistent with the review by Sindaco et al, where it is described that, in patients with ALL, IL-15 is overexpressed. This increase was associated with disease severity and a greater risk of infiltration to the central nervous system due to PSGL-1 and CXCR3 regulation which attract malignant cells to the central nervous system [ 22 ]. Contrary to what was found in our population, Wadai found a significant depletion in IL-15 levels in an Iraqi population of 21 patients with ALL compared to the healthy population [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of a Cross-Training and Resistance Exercise Routine on IL-15 in Adults with Type B Acute Lymphoblastic Leukemia during the Induction Phase: Randomized Pilot Study

Gallardo Rodríguez,

Olarte Carrillo,

Martínez Tovar

et al. 2023

JFMK

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IL-15 is a proinflammatory myokine essential for activating NK cells and CD8+ T lymphocytes, and its overexpression has been related to reducing overall survivorship in patients with acute lymphoblastic leukemia (ALL). Physical exercise has been shown to be safe, feasible, and beneficial in hematological cancers. Exercise requires the activation of muscles that secrete cytokines, such as IL-15, causing immune mobilization. The objective was to compare the outcomes of two training routines on IL-15 and survival prognosis in adult patients diagnosed with ALL. A blind randomized clinical study was carried out where twenty-three peripheral blood samples were obtained pre and postexercise intervention from patients categorized into three types of intervention: the resistance exercise group (REG), the cross-training exercise group (CEG), and the control group (CG). Changes in IL-15 levels during the intervention were not significant in any of the groups (CG p = 0.237, REG p = 0.866, and CEG p = 0.678). However, 87.5% of patients who received an exercise intervention achieved remission, while only 21.73% experienced a relapse. There were no deaths during the study. Although IL-15 level adaptation in the REG and the CG performed similarly, the REG induced a better clinical outcome. Resistance exercises may help improve survival prognosis and reduce relapses in patients with ALL.

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“…Of note, the g-chain cytokine IL-15 was shown to signal from pPCs in an autocrine manner to pPCs and in a paracrine manner to cPCs by binding the common cytokine receptor γ chain (γc or CD132; encoded by the IL2RG gene) in the immunoparesis-nega(ve sekng. Conversely, in immunoparesis-posi(ve pa(ents, this cytokine signals from cPCs to cPCs and pPCs through the IL15RA receptor [58][59][60][61] . Only in this laZer sekng, the downstream signalling involves ac(va(on of pro-inflammatory pathways.…”

Section: The Interactome Landscape Of Immunoparesis In Polyclonal Pcsmentioning

confidence: 99%

Genotypic identification of polyclonal plasma cells in plasma cell dyscrasias shows an aberrant single-cell phenotype with clinical implications

Da Vià,

Lazzaroni,

Matera

et al. 2024

Preprint

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Multiple Myeloma (MM) is driven by clonal plasma cell (PC)-intrinsic factors and changes in the tumorigenic microenvironment (TME). To investigate if residual polyclonal PCs (pPCs) are disrupted, single-cell (sc) RNAseq and sc B-cell receptor analysis were applied in a cohort of 46 samples with PC dyscrasias and 18 healthy donors (HDs). Out of n=213,074 CD138pos PCs, 42,717 were genotypically identified as pPCs. Compared to HDs, we detected quantitative and qualitative differences in pPCs of patients showing immunoparesis, where we showed a pro-inflammatory status, driven by specific cellular interactions with TME. Finally, we derived a "hPC signature" that, once inferred in the CoMMpass dataset, was predictive of PFS and OS. Our findings show that genotypic, single-cell identification of pPCs in PC dyscrasias has relevant pathogenic and clinical implications.

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The role of interleukin-15 in the development and treatment of hematological malignancies

Cited by 10 publications

References 144 publications

In vitro IL-15-activated human naïve CD8+ T cells down-modulate the CD8β chain and become CD8αα T cells

In vitro IL-15-activated human naïve CD8+ T cells down-modulate the CD8β chain and become CD8αα T cells

Effect of a Cross-Training and Resistance Exercise Routine on IL-15 in Adults with Type B Acute Lymphoblastic Leukemia during the Induction Phase: Randomized Pilot Study

Genotypic identification of polyclonal plasma cells in plasma cell dyscrasias shows an aberrant single-cell phenotype with clinical implications

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