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      A Nobel Prize-worthy pursuit: cancer immunology and harnessing immunity to tumour neoantigens

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      Immunology
      Wiley

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          Abstract

          <p id="d117505e120">The field of cancer immunology stepped into the limelight this year when James P. Allison and Tasuku Honjo received the Nobel Prize in Physiology or Medicine for their discovery of cancer therapy by inhibition of negative immune regulation. Among many exciting advances contributing to the coming of age of tumour immunology as a viable clinical specialty has been the ability to progress from the initial elucidation of tumour antigens, such as the melanoma antigen, <span style="fixed-case">MAGE</span>‐1, to high‐throughput sequencing facilitating identification of T cell epitopes from diverse tumour neoantigens. This has resulted from the convergence of expertise in tumour biology, next‐generation sequencing, T cell and structural immunology, and predictive algorithms. Among many examples, immunotherapy for ovarian cancer has been one of the beneficiaries of these advances, leading to a number of recent and ongoing clinical trials. </p>

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          Most cited references5

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          Is Open Access

          Cancer immunotherapy: the beginning of the end of cancer?

          These are exciting times for cancer immunotherapy. After many years of disappointing results, the tide has finally changed and immunotherapy has become a clinically validated treatment for many cancers. Immunotherapeutic strategies include cancer vaccines, oncolytic viruses, adoptive transfer of ex vivo activated T and natural killer cells, and administration of antibodies or recombinant proteins that either costimulate cells or block the so-called immune checkpoint pathways. The recent success of several immunotherapeutic regimes, such as monoclonal antibody blocking of cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD1), has boosted the development of this treatment modality, with the consequence that new therapeutic targets and schemes which combine various immunological agents are now being described at a breathtaking pace. In this review, we outline some of the main strategies in cancer immunotherapy (cancer vaccines, adoptive cellular immunotherapy, immune checkpoint blockade, and oncolytic viruses) and discuss the progress in the synergistic design of immune-targeting combination therapies.
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            The impact of inflationary cytomegalovirus-specific memory T cells on anti-tumour immune responses in patients with cancer

            Human cytomegalovirus ( CMV ) is a ubiquitous, persistent beta herpesvirus. CMV infection contributes to the accumulation of functional antigen‐specific CD 8 + T‐cell pools with an effector‐memory phenotype and enrichment of these immune cells in peripheral organs. We review here this ‘memory T‐cell inflation’ phenomenon and associated factors including age and sex. ‘Collateral damage’ due to CMV ‐directed immune reactivity may occur in later stages of life – arising from CMV ‐specific immune responses that were beneficial in earlier life. CMV may be considered an age‐dependent immunomodulator and a double‐edged sword in editing anti‐tumour immune responses. Emerging evidence suggests that CMV is highly prevalent in patients with a variety of cancers, particularly glioblastoma. A better understanding of CMV ‐associated immune responses and its implications for immune senescence, especially in patients with cancer, may aid in the design of more clinically relevant and tailored, personalized treatment regimens. ‘Memory T‐cell inflation’ could be applied in vaccine development strategies to enrich for immune reactivity where long‐term immunological memory is needed, e.g. in long‐term immune memory formation directed against transformed cells.
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              Nature of tumour rejection antigens in ovarian cancer

              Major progress in the analysis of human immune responses to cancer has been made through the molecular characterization of human tumour antigens. The development of therapeutic strategies for eliciting immune‐mediated rejection of tumours has accelerated due to the elucidation of the molecular basis for tumour cell recognition and destruction by immune cells. Of the various human tumour antigens defined to date in ovarian cancer, the cancer‐testis ( CT ) family of antigens have been studied extensively preclinically and clinically because of their testis‐restricted expression in normal tissues and ability to elicit robust immune responses. Recent developments in cancer sequencing technologies offer a unique opportunity to identify tumour mutations with the highest likelihood of being expressed and recognized by the immune system. Such mutations, or neoantigens, could potentially serve as specific immune targets for T‐cell‐mediated destruction of cancer cells. This review will highlight current work in selecting tumour rejection antigens in ovarian cancer for improving the efficacy of immunotherapy.
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                Author and article information

                Journal
                Immunology
                Immunology
                Wiley
                00192805
                November 2018
                November 2018
                October 15 2018
                : 155
                : 3
                : 283-284
                Affiliations
                [1 ]Department of Medicine; Hammersmith Hospital; London UK
                Article
                10.1111/imm.13008
                6187215
                30320408
                755652cb-7d1b-44ed-a6ab-37996d4e5725
                © 2018

                http://doi.wiley.com/10.1002/tdm_license_1.1

                http://onlinelibrary.wiley.com/termsAndConditions#vor

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