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      Roles of the immune system in cancer: from tumor initiation to metastatic progression

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          Abstract

          In this review, Gonzelez et al. provide an update of recent accomplishments, unifying concepts, and futures challenges to study tumor-associated immune cells, with an emphasis on metastatic carcinomas.

          Abstract

          The presence of inflammatory immune cells in human tumors raises a fundamental question in oncology: How do cancer cells avoid the destruction by immune attack? In principle, tumor development can be controlled by cytotoxic innate and adaptive immune cells; however, as the tumor develops from neoplastic tissue to clinically detectable tumors, cancer cells evolve different mechanisms that mimic peripheral immune tolerance in order to avoid tumoricidal attack. Here, we provide an update of recent accomplishments, unifying concepts, and future challenges to study tumor-associated immune cells, with an emphasis on metastatic carcinomas.

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          Most cited references240

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          Hallmarks of Cancer: The Next Generation

          The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
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            The blockade of immune checkpoints in cancer immunotherapy.

            Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
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              Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012.

              Estimates of the worldwide incidence and mortality from 27 major cancers and for all cancers combined for 2012 are now available in the GLOBOCAN series of the International Agency for Research on Cancer. We review the sources and methods used in compiling the national cancer incidence and mortality estimates, and briefly describe the key results by cancer site and in 20 large "areas" of the world. Overall, there were 14.1 million new cases and 8.2 million deaths in 2012. The most commonly diagnosed cancers were lung (1.82 million), breast (1.67 million), and colorectal (1.36 million); the most common causes of cancer death were lung cancer (1.6 million deaths), liver cancer (745,000 deaths), and stomach cancer (723,000 deaths). © 2014 UICC.
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                Author and article information

                Journal
                Genes Dev
                Genes Dev
                genesdev
                genesdev
                GAD
                Genes & Development
                Cold Spring Harbor Laboratory Press
                0890-9369
                1549-5477
                1 October 2018
                : 32
                : 19-20
                : 1267-1284
                Affiliations
                Department of Anatomy, the Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California 94143, USA
                Author notes
                [1]

                Present address: Department of Clinical Genetics, Lund University, SE-221 85 Lund, Sweden.

                Corresponding author: zena.werb@ 123456ucsf.edu
                Author information
                http://orcid.org/0000-0002-6525-3872
                Article
                8711660
                10.1101/gad.314617.118
                6169832
                30275043
                7f0e2a1a-4cc7-420a-ae91-59e31ee39c06
                © 2018 Gonzalez et al.; Published by Cold Spring Harbor Laboratory Press

                This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

                History
                Page count
                Pages: 18
                Funding
                Funded by: National Cancer Institute , open-funder-registry 10.13039/100000054;
                Award ID: R01 CA057621
                Award ID: U01 CA190851
                Funded by: Parker Institute for Cancer Immunotherapy
                Funded by: Becas Chile
                Funded by: Tegger Foundation
                Funded by: Wenner-Gren Foundations
                Funded by: Sweden-America Foundation , open-funder-registry 10.13039/501100001727;
                Funded by: Swedish Society of Medicine , open-funder-registry 10.13039/501100007687;
                Funded by: Swedish Society for Medical Research , open-funder-registry 10.13039/501100003748;
                Categories
                7
                9
                Review

                disseminated tumor cells,tumor-associated macrophages,metastasis-associated immune cells,patient-derived xenograft,immune cross-talk,cancer heterogeneity

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