ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011
Interleukin-7 inhibits tumor-induced CD27-CD28- suppressor T cells: implications for cancer immunotherapy.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
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- Breaking barriers: Smart vaccine platforms for cancer immunomodulation.Cancer communications (London, England) · 2025Review
- Senescent T Cells: The Silent Culprit in Acute Myeloid Leukemia Progression?International journal of molecular sciences · 2024Review
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- Theranostic signature of tumor-derived exosomes in cancer.Medical oncology (Northwood, London, England) · 2023Review
- The immunome of mobilized peripheral blood stem cells is predictive of long-term outcomes and therapy-related myeloid neoplasms in patients with multiple myeloma undergoing autologous stem cell transplant.Blood cancer journal · 2023Article
- Communicator Extraordinaire: Extracellular Vesicles in the Tumor Microenvironment Are Essential Local and Long-Distance Mediators of Cancer Metastasis.Biomedicines · 2023Review
- A high OXPHOS CD8 T cell subset is predictive of immunotherapy resistance in melanoma patients.The Journal of experimental medicine · 2022Article
- Exosomes as smart drug delivery vehicles for cancer immunotherapy.Frontiers in immunology · 2022Review
- Extracellular Vesicles and Cancer Stem Cells in Tumor Progression: New Therapeutic Perspectives.International journal of molecular sciences · 2021Review
- Exercise and the immune system: taking steps to improve responses to cancer immunotherapy.Journal for immunotherapy of cancer · 2021Review
- Tumor-Derived Exosomes in Immunosuppression and Immunotherapy.Journal of immunology research · 2020Review
- Immune-Checkpoint Blockade Opposes CD8Cancer immunology research · 2019Article
- Tumor-derived exosomes induce CD8Journal for immunotherapy of cancer · 2017Article
- Mcl-1 regulates reactive oxygen species via NOX4 during chemotherapy-induced senescence.Oncotarget · 2017Article
- T cells in multiple myeloma display features of exhaustion and senescence at the tumor site.Journal of hematology & oncology · 2016Article
- Effector, Memory, and Dysfunctional CD8(+) T Cell Fates in the Antitumor Immune Response.Journal of immunology research · 2016Review
- Common gamma chain cytokines in combinatorial immune strategies against cancer.Immunology letters · 2016Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
purposeWe have previously reported that many types of tumors can induce changes in human T cells that lead to the acquisition of suppressive function and phenotypic alterations resembling those found in senescent T cells. In the present study, we find a role for interleukin 7 (IL-7) in protecting T cells from these changes and further define involved signaling pathways. EXPERIMENTAL
designWe evaluated the ability of IL-7 treatment to prevent the gain of suppressive function and phenotypic alterations in human T cells after a short coculture with tumor cells in vitro. We then used inhibitors of components of the phosphoinositide 3-kinase (PI3K)/AKT pathway and short interfering RNA knockdown of Mcl-1 and Bim to evaluate the role of these signaling pathways in IL-7 protection.
resultsWe found that IL-7 inhibits CD27/CD28 loss and maintains proliferative capacity, IL-2 production, and reduced suppressive function. The protective ability of IL-7 depended on activation of the PI3K/AKT pathway, which inhibited activation of glycogen synthase kinase 3β, which, in turn, prevented the phosphorylation and loss of Mcl-1. We further showed a key role for Mcl-1 in that its knockdown or inhibition abrogated the effects of IL-7. In addition, knockdown of the Mcl-1 binding partner and proapoptotic protein Bim protected T cells from these dysfunctional alterations.
conclusionThese observations confirm the role for Bcl-2 family members in cytokine signaling and suggest that IL-7 treatment in combination with other immunotherapies could lead to new clinical strategies to maintain normal T-cell function and reduce tumor-induced generation of dysfunctional and suppressor T cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.