An overview of IL-7 biology and its use in immunotherapy

El-Kassar, Nahed; Gress, Ronald E.

doi:10.3109/15476910903453296

Cited by 96 publications

(79 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IL‐7, another common gamma γ c cytokine, is also considered for use in cancer and chronic viral infections, highlighting the potential in immunotherapies. This is particularly important in the carinogenic trematodes, S. haematobium, Opisthorchis viverrini and Clonorchis sinensis where one of the pathological manifestations of these infections is cancer in different organs (bladder, bile duct and liver) for which we currently do not have any therapeutic interventions beyond surgery.…”

Section: Modulating Ilc2 Responsesmentioning

confidence: 99%

Group 2 ILCs: A way of enhancing immune protection against human helminths?

Nausch

Mutapi

2017

Parasite Immunology

View full text Add to dashboard Cite

SummaryGroup 2 innate lymphoid cells (ILC2s) play crucial roles in type 2 immune responses associated with allergic and autoimmune diseases, viral and helminth infections and tissue homoeostasis. Experimental models show that in helminth infections ILC2s provide an early source of type 2 cytokines and therefore are essential for the induction of potentially protective type 2 responses. Much of our knowledge of ILC2s in helminth infections has come from experimental mouse models with very few studies analysing ILC2s in natural human infections. In attempts to harness knowledge from paradigms of the development of protective immunity in human helminth infections for vaccine development, the role of ILC2 cells could be pivotal. So far, potential vaccines against human helminth infections have failed to provide effective protection when evaluated in human studies. In addition to appropriate antigen selection, it is apparent that more detailed knowledge on mechanisms of induction and maintenance of protective immune responses is required. Therefore, there is need to understand how ILC2 cells induce type 2 responses and subsequently support the development of a protective immune response in the context of immunizations. Within this review, we summarize the current knowledge of the biology of ILC2s, discuss the importance of ILC2s in human helminth infections and explore how ILC2 responses could be boosted to efficiently induce protective immunity.

show abstract

Section: Modulating Ilc2 Responsesmentioning

confidence: 99%

Group 2 ILCs: A way of enhancing immune protection against human helminths?

Nausch

Mutapi

2017

Parasite Immunology

View full text Add to dashboard Cite

show abstract

“…Accordingly, recombinant IL-7 has been suggested as a potential therapeutic agent in patients with lymphopaenia [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

T cell Reconstitution in Allogeneic Haematopoietic Stem Cell Transplantation: Prognostic Significance of Plasma Interleukin‐7

et al. 2014

View full text Add to dashboard Cite

Infections and acute graft-versus-host disease (aGVHD) are major causes of treatment-related mortality and morbidity following allogeneic haematopoietic stem cell transplantation (HSCT). Both complications depend on reconstitution of the T-lymphocyte population based on donor T cells. Although it is well established that Interleukin-7 (IL-7) is a cytokine essential for de novo T cell development in the thymus and homoeostatic peripheral expansion of T cells, associations between circulating levels of IL-7 and T cell reconstitution following HSCT have not been investigated previously. We prospectively measured IL-7 levels in 81 patients undergoing myeloablative HSCT with either sibling donor or an unrelated donor. Plasma IL-7 levels peaked at day +7 post-transplant (1.3-82.4 pg/ml), at the time of maximal lymphopaenia. In multivariate analysis, peak levels of IL-7 were significantly higher in patients treated with antithymocyte globulin (ATG) compared with those not treated with ATG (P = 0.0079). IL-7 levels at day +7 were negatively associated with T cell counts at day +30 to +60 (at day +60: CD3 + : b = À10.6 9 10 6 cells/l, P = 0.0030; CD8 + : b = À8.4 9 10 6 cells/l, P = 0.061; CD4 + : b = À2.1 9 10 6 cells/l, P = 0.062) in multivariate analyses. In adults, high IL-7 levels were associated with increased risk of grade II-IV aGVHD (OR = 5.4, P = 0.036) and reduced overall survival (P = 0.046). The present data indicate that high plasma levels of IL-7 in the early post-transplant period are predictive for slow T cell reconstitution, increased risk of aGVHD and increased mortality following HSCT.

show abstract

“…The preclinical and clinical application of rIL‐7 has been reported to result in enhanced T‐cell immunity, raising the prospect that IL‐7 signaling could mediate therapeutic benefits in the treatment of acute and chronic infections and cancer . Given the published clinical experience with the use of rhIL‐7 therapy so far is modest, enhancing IL‐7Rα by targeting CD27 may synergize with rhIL‐7 therapy to achieve optimized IL‐7 signaling especially in the elderly, leading to more favorable outcomes. Moreover, in comparison to rhIL‐7 therapy that primarily targets steady‐state T‐cell populations and improves immune reconstitution through increasing thymic output and through Ag‐independent homeostatic driven proliferation in the periphery, CD27 stimulation promotes IL‐7Rα in effector CD8 + T‐cell population in an Ag‐dependent manner and contributes to their long‐term maintenance.…”

Section: Discussionmentioning

confidence: 99%

Frontline Science: Late CD27 stimulation promotes IL-7Rα transcriptional re-expression and memory T cell qualities in effector CD8+ T cells

Dong

Buckner

Prince

et al. 2019

Journal of Leukocyte Biology

View full text Add to dashboard Cite

We previously demonstrated that CD27 co-stimulation during a primary CD8+ T cell response was critical for the expression of IL-7Rα on acute effector CD8+ T cells, providing an essential element in the generation of CD8+ T cell memory to infectious pathogens. IL-7 plays a critical role in the generation and maintenance of memory CD8+ T cells, and IL-7Rα has been regarded as a functional marker of long-lived memory precursor effector cells. While IL-7Rα is down-regulated acutely upon TCR stimulation, the regulation of the emergence of IL-7Rα expressing cells around the peak of primary CD8+ responses is less clear. Re-expression could be a default outcome after withdrawal of TCR stimulation. Alternatively, specific stimuli actively antagonize the down-regulation or promote the recovery of IL-7Rα in Ag-activated CD8+ T cells. By utilizing agonistic mAb and transgenic models, here we show: 1) CD27 stimulation acts directly on CD8+ T cells to enhance IL-7Rα-expressing effectors; 2) CD27 stimulation neither alleviates the down-regulation of IL-7Rα upon TCR signaling nor promotes the expansion/survival of IL-7Rα-expressing effectors, but facilitates IL-7Rα re-expression; 3) CD27 stimulation regulates Il7ra mRNA abundance but not protein distribution. Importantly, CD27 stimulation promotes not only IL-7Rα, but also the common γ chain of the receptor and the downstream signaling mediated by pSTAT5. Our results demonstrate a previously unappreciated role of CD27 stimulation as a positive regulator of IL-7Rα during CD8 T cell responses, provide insights into the mechanistic basis by which CD27 stimulation influences CD8+ T cell memory differentiation, and highlight the potential of targeting CD27-CD70 axis to enhance IL-7 signaling for antiviral/antitumor immunotherapy.

show abstract

An overview of IL-7 biology and its use in immunotherapy

Cited by 96 publications

References 61 publications

Group 2 ILCs: A way of enhancing immune protection against human helminths?

Group 2 ILCs: A way of enhancing immune protection against human helminths?

T cell Reconstitution in Allogeneic Haematopoietic Stem Cell Transplantation: Prognostic Significance of Plasma Interleukin‐7

Frontline Science: Late CD27 stimulation promotes IL-7Rα transcriptional re-expression and memory T cell qualities in effector CD8+ T cells

Contact Info

Product

Resources

About