Interleukin-21 restrains tumor growth and induces a substantial increase in the number of circulating tumor-specific T cells in a murine model of malignant melanoma

Petersen, Charlotte Christie; Diernaes, Jon Erik Fraes; Skovbo, Anni; Hvid, Malene; Hokland, Marianne

doi:10.1016/j.cyto.2009.11.001

Cited by 12 publications

(4 citation statements)

References 44 publications

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“…Mice with established subcutaneous melanoma treated with IL-21 demonstrated an increase in circulating anti-tumor T cells 4–7 days after chemoimmunotherapy [107]. However, recent findings suggest IL-21 promote Th17 differentiation and IL-10 production, but it may also suppress pathogenic T cell subset Th1/17 that co-produce IFN-γ and GM-CSF.…”

Section: Use Of γChain Cytokines In Solid Cancersmentioning

confidence: 99%

Common gamma chain cytokines in combinatorial immune strategies against cancer

et al. 2016

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Common γ chain (γC) cytokines, namely IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21 are important for the proliferation, differentiation, and survival of lymphocytes that display antitumor activity, thus stimulating considerable interest for the use of cytokines in cancer immunotherapy. In this review, we will focus on the γC cytokines that demonstrate the greatest potential for immunotherapy, IL-2, IL-7, IL-15, and IL-21. We will briefly cover their biological function, potential applications in cancer therapy, and update on their use in combinatorial immune strategies for eradicating tumors and hematopoietic malignancies.

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Section: Use Of γChain Cytokines In Solid Cancersmentioning

confidence: 99%

Common gamma chain cytokines in combinatorial immune strategies against cancer

et al. 2016

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“…IL-21 exerts a wide range of biological effects on several cell types and has been shown to elicit antitumor activity in preclinical models of melanoma (also see Figure 1 & Table 1) [149]. It promotes proliferation and antibody iso-type switching in B lymphocytes, which have been preactivated through CD40 ligands [150], but induces apoptosis in naive B cells and in those that have been activated through Toll-like receptor (TLR)4 or TLR9 ligands [151].…”

Section: Malignant Melanomamentioning

confidence: 99%

Immunomodulatory Cytokines as Therapeutic Agents for Melanoma

Nicholas

Lesinski²

2011

Immunotherapy

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Melanoma is the most aggressive form of skin cancer whose worldwide incidence is rising faster than any other cancer. Few treatment options are available to patients with metastatic disease, and standard chemotherapeutic agents are generally ineffective. Cytokines such as IFN-α or IL-2 can promote immune recognition of melanoma, occasionally inducing dramatic and durable clinical responses. Here, we discuss several immunomodulatory agents, the safety of which are being evaluated in clinical trials. Challenges include an incomplete understanding of signaling pathways, appropriate clinical dose and route, and systemic immunosuppression in advanced melanoma patients. We consider how targeted cytokine therapy will integrate into the clinical arena, as well as the low likelihood of success of single cytokine therapies. Evidence supports a synergy between cytokine immunotherapy and other therapeutic approaches in melanoma, and strengthening this area of research will improve our understanding of how to use cytokine therapy better.

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“…87,88 The capacity of IL-21 to direct differentiation of inflammatory CD4 + T cells while inhibiting Tregs and enhancing cytolytic function of CD8 and NK cells makes it an attractive cytokine for use in cancer immunotherapy. IL-21 treatment can inhibit growth of syngeneic tumors including Rena renal carcinoma and B16 melanoma, both with 89 and without 90,91 adoptive transfer of tumor-specific T cells. Similarly, antitumor effects have been observed in several models where murine tumors were genetically modified to secrete IL-21.…”

Section: Interleukin-21 Il-21 Biology and Preclinical Studiesmentioning

confidence: 99%

Novel Gamma-Chain Cytokines as Candidate Immune Modulators in Immune Therapies for Cancer

Fewkes¹,

Mackall²

2010

The Cancer Journal

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Cytokines that signal through the common-gamma chain are potent growth factors for T cells and natural killer cells. Interleukin (IL)-2, the gammac prototype, can mediate antitumor effects as a single agent or in the context of multimodality regimens but is limited by side effects and a propensity for expansion of regulatory T cells. IL-7, IL-15, and IL-21 each possess properties that can be exploited in the context of immunotherapy for cancer. Each has been demonstrated to mediate potent vaccine adjuvant effects in tumor models, and each can enhance the effectiveness of adoptive immunotherapies. Although the overlap among the agents is significant, IL-7 is uniquely immunorestorative and preferentially augments reactivity of naive populations, IL-15 potently augments reactivity of CD8 memory cells and natural killer cells, and IL-21 preferentially expands the inflammatory Th17 subset and may limit terminal differentiation of effector CD8 cells. Clinical trials of IL-7 and IL-21 have already been completed and, so far, demonstrate safety and biologic activity of these agents. Clinical trials of IL-15 are expected soon. Ultimately, these agents are expected to be most effective in the context of multimodal immunotherapy regimens, and careful clinical trial design will be needed to efficiently identify the proper doses, regimens, and settings in which to exploit their biologic properties for therapeutic gain.

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Interleukin-21 restrains tumor growth and induces a substantial increase in the number of circulating tumor-specific T cells in a murine model of malignant melanoma

Cited by 12 publications

References 44 publications

Common gamma chain cytokines in combinatorial immune strategies against cancer

Common gamma chain cytokines in combinatorial immune strategies against cancer

Immunomodulatory Cytokines as Therapeutic Agents for Melanoma

Novel Gamma-Chain Cytokines as Candidate Immune Modulators in Immune Therapies for Cancer

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