Common gamma chain cytokines and CD8 T cells in cancer

Shourian, Mitra; Beltra, Jean-Christophe; Bourdin, Benoîte; Decaluwe, Hélène

doi:10.1016/j.smim.2019.101307

Cited by 31 publications

(25 citation statements)

References 284 publications

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“…It is a member of the common receptor gamma chain (γ c ) family, which also includes IL-2, IL-4, IL-7, IL-9, and IL-21. This group of cytokines has broad pleiotropic activity on both the innate and adaptive immune systems, with important therapeutic ramifications, reviewed elsewhere [1,2]. IL-15 signals through a receptor complex composed of the IL-2/IL-15 receptor β (CD122) and the common γ c receptor subunit (CD132), also shared by all other family members [3].…”

Section: Introductionmentioning

confidence: 99%

Rationale for IL-15 superagonists in cancer immunotherapy

Knudson

Hodge

Schlom

et al. 2020

Expert Opinion on Biological Therapy

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Section: Introductionmentioning

confidence: 99%

Rationale for IL-15 superagonists in cancer immunotherapy

Knudson

Hodge

Schlom

et al. 2020

Expert Opinion on Biological Therapy

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“…5 In our systemic search for a potent cytokine that can arm oncolytic vaccinia virus to maximize their therapeutic efficacy, we had been considering IL-21 as an important candidate. As a member of the common gamma-chain (γc) family of cytokines, IL-21 is mainly secreted by activated CD4 + T cells and natural killer T (NKT) cells, 11 and plays a pleiotropic role in regulating multiple types of immune cells, including B cells, T cells, natural killer (NK) cells and monocyte-derived DCs. 12 Accordingly, IL-21 has been shown to possess tumor suppressor activity and, in a B16 melanoma model, its local administration conferred more potent antitumor efficacy than subcutaneous injection, leading to prolonged survival in treated mice.…”

Section: Introductionmentioning

confidence: 99%

IL-21 arming potentiates the anti-tumor activity of an oncolytic vaccinia virus in monotherapy and combination therapy

Chen

Ding

Liao

et al. 2021

J Immunother Cancer

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BackgroundOncolytic viruses (OVs) have shown promise in containing cancer progression in both animal models and clinical trials. How to further improve the efficacy of OVs are intensively explored. Arming OVs with immunoregulatory molecules has emerged as an important means to enhance their oncolytic activities majorly based on the mechanism of reverting the immunosuppressive nature of tumor environment. In this study, we aimed to identify the optimal combination of different OVs and immunomodulatory molecules for solid tumor treatment as well as the underlying mechanism, and subsequently evaluated its potential synergy with other immunotherapies.MethodsPanels of oncolytic viruses and cells stably expressing immunoregulatory molecules were separately evaluated for treating solid tumors in mouse model. A tumor-targeted replicating vaccinia virus Tian Tan strain with deletion of TK gene (TTVΔTK) was armed rationally with IL-21 to create rTTVΔTK-IL21 through recombination. CAR-T cells and iNKT cells were generated from human peripheral blood mononuclear cells. The impact of rTTVΔTK-IL21 on tumor-infiltrating lymphocytes was assessed by flow cytometry, and its therapeutic efficacy as monotherapy or in combination with CAR-T and iNKT therapy was assessed in mouse tumor models.ResultsIL-21 and TTV was respectively identified as most potent immunomodulatory molecule and oncolytic virus for solid tumor suppression in mouse models. A novel recombinant oncolytic virus that resulted from their combination, namely rTTVΔTK-mIL21, led to significant tumor regression in mice, even for noninjected distant tumor. Mechanistically, rTTV∆TK-mIL21 induced a selective enrichment of immune effector cells over Treg cells and engage a systemic response of therapeutic effect. Moreover, its human form showed a notable synergy with CAR-T or iNKT therapy for tumor treatment when coupled in humanized mice.ConclusionWith a strong potency of shaping tumor microenvironment toward favoring TIL activities, rTTVΔTK-IL21 represents a new opportunity worthy of further exploration in clinical settings for solid tumor control, particularly in combinatorial strategies with other immunotherapies.One sentence summaryIL21-armed recombinant oncolytic vaccinia virus has potent anti-tumor activities as monotherapy and in combination with other immunotherapies.

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“…In particular, the common gamma chain (γ c or CD132) family of cytokines, especially IL-2, IL-7, IL-15, and IL-21, have been actively explored for improving the efficacy of cancer immunotherapies. 128 The receptors of these cytokines share the γc subunit that forms dimeric or trimeric receptor complexes mediating signaling that promotes the survival, proliferation, effector/memory generation and maintenance of T cells. 128,129 Among the γc family cytokines, IL-15 is unique in that it requires a transpresentation mechanism to engage its receptor for signal stimulation.…”

Section: Cytokine Signalingmentioning

confidence: 99%

“…128 The receptors of these cytokines share the γc subunit that forms dimeric or trimeric receptor complexes mediating signaling that promotes the survival, proliferation, effector/memory generation and maintenance of T cells. 128,129 Among the γc family cytokines, IL-15 is unique in that it requires a transpresentation mechanism to engage its receptor for signal stimulation. 130 IL-15 receptor (IL-15R) is composed of three submits: IL-15Rα, IL-15Rβ (also called IL-2Rβ or CD122), and γc.…”

Section: Cytokine Signalingmentioning

confidence: 99%

Targeting ubiquitin signaling for cancer immunotherapy

Zhou

Sun

2021

Sig Transduct Target Ther

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Cancer immunotherapy has become an attractive approach of cancer treatment with tremendous success in treating various advanced malignancies. The development and clinical application of immune checkpoint inhibitors represent one of the most extraordinary accomplishments in cancer immunotherapy. In addition, considerable progress is being made in understanding the mechanism of antitumor immunity and characterizing novel targets for developing additional therapeutic approaches. One active area of investigation is protein ubiquitination, a post-translational mechanism of protein modification that regulates the function of diverse immune cells in antitumor immunity. Accumulating studies suggest that E3 ubiquitin ligases and deubiquitinases form a family of potential targets to be exploited for enhancing antitumor immunity in cancer immunotherapy.

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Common gamma chain cytokines and CD8 T cells in cancer

Cited by 31 publications

References 284 publications

Rationale for IL-15 superagonists in cancer immunotherapy

Rationale for IL-15 superagonists in cancer immunotherapy

IL-21 arming potentiates the anti-tumor activity of an oncolytic vaccinia virus in monotherapy and combination therapy

Targeting ubiquitin signaling for cancer immunotherapy

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