. 2014 Oct; 6(7):833-52.
doi: 10.2217/imt.14.51.

Targeting CD8+ T-cell tolerance for cancer immunotherapy

Stephanie R Jackson 1 Jinyun Yuan  Ryan M Teague  
  • PMID: 25290416
  •     144 References
  •     24 citations


In the final issue of Science in 2013, the American Association of Science recognized progress in the field of cancer immunotherapy as the 'Breakthrough of the Year.' The achievements were actually twofold, owing to the early success of genetically engineered chimeric antigen receptors (CAR) and to the mounting clinical triumphs achieved with checkpoint blockade antibodies. While fundamentally very different, the common thread of these independent strategies is the ability to prevent or overcome mechanisms of CD8(+) T-cell tolerance for improved tumor immunity. Here we discuss how circumventing T-cell tolerance has provided experimental insights that have guided the field of clinical cancer immunotherapy to a place where real breakthroughs can finally be claimed.

Keywords: CD8+ T-cell checkpoint blockade; adoptive cell transfer; cancer immunotherapy; cancer vaccine; chimeric antigen receptor; lymphodepletion; tolerance.

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Immunol Rev, 2013 Dec 18; 257(1). PMID: 24329791
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Nat Immunol, 2007 Feb 17; 8(3). PMID: 17304234
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IL-12 release by engineered T cells expressing chimeric antigen receptors can effectively Muster an antigen-independent macrophage response on tumor cells that have shut down tumor antigen expression.
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Re-adapting T cells for cancer therapy: from mouse models to clinical trials.
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Studies on the immunological response to foreign tumor transplants in the mouse. I. The role of lymph node cells in conferring immunity by adoptive transfer.
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Recombinant AAV-CEA Tumor Vaccine in Combination with an Immune Adjuvant Breaks Tolerance and Provides Protective Immunity.
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Boosting the Immune Response with the Combination of Electrochemotherapy and Immunotherapy: A New Weapon for Squamous Cell Carcinoma of the Head and Neck?
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Defining muscle-invasive bladder cancer immunotypes by introducing tumor mutation burden, CD8+ T cells, and molecular subtypes.
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Robust antigen-specific CD8 T cell tolerance to a model prostate cancer neoantigen.
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A Palette of Cytokines to Measure Anti-Tumor Efficacy of T Cell-Based Therapeutics.
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The interplay between cancer associated fibroblasts and immune cells in the context of radiation therapy.
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Robust Prediction of Immune Checkpoint Inhibition Therapy for Non-Small Cell Lung Cancer.
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Cisplatin remodels the tumor immune microenvironment via the transcription factor EB in ovarian cancer.
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