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      Restoring the Immunity in the Tumor Microenvironment: Insights into Immunogenic Cell Death in Onco-Therapies

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          Abstract

          Simple Summary

          Since the role of immune evasion was included as a hallmark in cancer, the idea of cancer as a single cell mass that replicate unlimitedly in isolation was dissolved. In this sense, cancer and tumorigenesis cannot be understood without taking into account the tumor microenvironment (TME) that plays a crucial role in drug resistance. Immune characteristics of TME can determine the success in treatment at the same time that antitumor therapies can reshape the immunity in TME. Here, we collect a variety of onco-therapies that have been demonstrated to induce an interesting immune response accompanying its pharmacological action that is named as “immunogenic cell death”. As this report shows, immunogenic cell death has been gaining importance in antitumor therapy and should be studied in depth as well as taking into account other applications that may arise from this immune phenomenon.

          Abstract

          Immunogenic cell death (ICD) elicited by cancer therapy reshapes the tumor immune microenvironment. A long-term adaptative immune response can be initiated by modulating cell death by therapeutic approaches. Here, the major hallmarks of ICD, endoplasmic reticulum (ER) stress, and damage-associated molecular patterns (DAMPs) are correlated with ICD inducers used in clinical practice to enhance antitumoral activity by suppressing tumor immune evasion. Approaches to monitoring the ICD triggered by antitumoral therapeutics in the tumor microenvironment (TME) and novel perspective in this immune system strategy are also reviewed to give an overview of the relevance of ICD in cancer treatment.

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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 Hallmarks of Cancer

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              Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018

              Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                05 June 2021
                June 2021
                : 13
                : 11
                : 2821
                Affiliations
                [1 ]Department of Medicine and General Cytometry Service-Nucleus, CIBERONC CB16/12/00400, Cancer Research Centre (IBMCC/CSIC/USAL/IBSAL), 37007 Salamanca, Spain; angytahg@ 123456usal.es (Á.-P.H.); pablojuanesvelasco@ 123456usal.es (P.J.-V.); alavi29@ 123456usal.es (A.L.-V.); halin.bareke@ 123456gmail.com (H.B.); emontalvillo@ 123456usal.es (E.M.); rgongora@ 123456usal.es (R.G.)
                [2 ]Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Institute of Health Sciences, Marmara University, 34722 Istanbul, Turkey
                [3 ]Proteomics Unit, Cancer Research Centre (IBMCC/CSIC/USAL/IBSAL), 37007 Salamanca, Spain
                Author notes
                [* ]Correspondence: mfuentes@ 123456usal.es ; Tel.: +34-923-294-811
                Author information
                https://orcid.org/0000-0002-5585-9918
                https://orcid.org/0000-0001-9435-2952
                https://orcid.org/0000-0002-8046-4301
                https://orcid.org/0000-0002-7305-3766
                Article
                cancers-13-02821
                10.3390/cancers13112821
                8201010
                34198850
                8bf9a51c-fd19-40a2-82f8-73c2764e29c1
                © 2021 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 ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 23 April 2021
                : 04 June 2021
                Categories
                Review

                immunogenic cell death,damps,apoptosis,necroptosis,autophagy,tumor microenvironment,natural products,chemotherapy,icd inducers,immunotherapy

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