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      Current Perspectives in Cancer Immunotherapy

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          Abstract

          Different immunotherapeutic approaches have proved to be of significant clinical value to many patients with different types of advanced cancer. However, we need more precise immunotherapies and predictive biomarkers to increase the successful response rates. The advent of next generation sequencing technologies and their applications in immuno-oncology has helped us tremendously towards this aim. We are now moving towards the realization of personalized medicine, thus, significantly increasing our expectations for a more successful management of the disease. Here, we discuss the current immunotherapeutic approaches against cancer, including immune checkpoint blockade with an emphasis on anti-PD-L1 and anti-CTLA-4 monoclonal antibodies. We also analyze a growing list of other co-inhibitory and co-stimulatory markers and emphasize the mechanism of action of the principal pathway for each of these, as well as on drugs that either have been FDA-approved or are under clinical investigation. We further discuss recent advances in other immunotherapies, including cytokine therapy, adoptive cell transfer therapy and therapeutic vaccines. We finally discuss the modulation of gut microbiota composition and response to immunotherapy, as well as how tumor-intrinsic factors and immunological processes influence the mutational and epigenetic landscape of progressing tumors and response to immunotherapy but also how immunotherapeutic intervention influences the landscape of cancer neoepitopes and tumor immunoediting.

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          Genetic instabilities in human cancers.

          Whether and how human tumours are genetically unstable has been debated for decades. There is now evidence that most cancers may indeed be genetically unstable, but that the instability exists at two distinct levels. In a small subset of tumours, the instability is observed at the nucleotide level and results in base substitutions or deletions or insertions of a few nucleotides. In most other cancers, the instability is observed at the chromosome level, resulting in losses and gains of whole chromosomes or large portions thereof. Recognition and comparison of these instabilities are leading to new insights into tumour pathogenesis.
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            NK cell recognition.

            The integrated processing of signals transduced by activating and inhibitory cell surface receptors regulates NK cell effector functions. Here, I review the structure, function, and ligand specificity of the receptors responsible for NK cell recognition.
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              Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions.

              Some tissue types give rise to human cancers millions of times more often than other tissue types. Although this has been recognized for more than a century, it has never been explained. Here, we show that the lifetime risk of cancers of many different types is strongly correlated (0.81) with the total number of divisions of the normal self-renewing cells maintaining that tissue's homeostasis. These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to "bad luck," that is, random mutations arising during DNA replication in normal, noncancerous stem cells. This is important not only for understanding the disease but also for designing strategies to limit the mortality it causes. Copyright © 2015, American Association for the Advancement of Science.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                30 September 2019
                October 2019
                : 11
                : 10
                : 1472
                Affiliations
                [1 ]Department of Life Sciences, School of Sciences, European University Cyprus, 1516 Nicosia, Cyprus; christofi.theodoulakis@ 123456ucy.ac.cy
                [2 ]Division of Surgery, School of Medicine, University of Crete, P.O. Box 2208, Voutes, 71003 Heraklion, Crete, Greece; vbaritak@ 123456gmail.com
                [3 ]Department of Biomedical and Biotechnological Sciences, Oncologic, Clinic and General Pathology Section, University of Catania, 95123 Catania, Italy; luca.falzone@ 123456unict.it (L.F.); m.libra@ 123456unict.it (M.L.)
                [4 ]Epidemiology Unit, IRCCS Istituto Nazionale Tumori “Fondazione G. Pascale”, 80131 Napoli, Italy
                [5 ]Research Center for Prevention, Diagnosis and Treatment of Cancer, University of Catania, 95123 Catania, Italy
                Author notes
                [* ]Correspondence: a.zaravinos@ 123456euc.ac.cy ; Tel.: +357-22559577
                Author information
                https://orcid.org/0000-0003-4625-5562
                Article
                cancers-11-01472
                10.3390/cancers11101472
                6826426
                31575023
                a5d0ca66-e7d9-4ba5-9c52-bb622128cb48
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 16 August 2019
                : 26 September 2019
                Categories
                Review

                immune checkpoint blockade,anti-pd-l1,anti-pd-1,anti-ctla-4,cytokine therapy,adoptive cell transfer,therapeutic vaccines

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