Abscopal Effect and Drug-Induced Xenogenization: A Strategic Alliance in Cancer Treatment?

The current state of cancer treatment is still far from being satisfactory considering the strong impairment of patients’ quality of life and the high lethality of malignant diseases. Therefore, it is critical for innovative approaches to be tested in the near future. In view of the crucial role tha...

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Published inInternational journal of molecular sciences Vol. 22; no. 19; p. 10672
Main Authors Franzese, Ornella, Torino, Francesco, Giannetti, Elisa, Cioccoloni, Giorgia, Aquino, Angelo, Faraoni, Isabella, Fuggetta, Maria Pia, De Vecchis, Liana, Giuliani, Anna, Kaina, Bernd, Bonmassar, Enzo
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 01.10.2021
MDPI
Subjects
Antigens
Brain cancer
Cancer therapies
Chemotherapy
Endocrine therapy
Immune response
Immunotherapy
Melanoma
Mutation
Radiation therapy
Review
Skin cancer
Tumors
Online AccessGet full text
ISSN1422-0067
1661-6596
1422-0067
DOI10.3390/ijms221910672

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Abstract The current state of cancer treatment is still far from being satisfactory considering the strong impairment of patients’ quality of life and the high lethality of malignant diseases. Therefore, it is critical for innovative approaches to be tested in the near future. In view of the crucial role that is played by tumor immunity, the present review provides essential information on the immune-mediated effects potentially generated by the interplay between ionizing radiation and cytotoxic antitumor agents when interacting with target malignant cells. Therefore, the radiation-dependent abscopal effect (i.e., a biological effect of ionizing radiation that occurs outside the irradiated field), the influence of cancer chemotherapy on the antigenic pattern of target neoplastic cells, and the immunogenic cell death (ICD) caused by anticancer agents are the main topics of this presentation. It is widely accepted that tumor immunity plays a fundamental role in generating an abscopal effect and that anticancer drugs can profoundly influence not only the host immune responses, but also the immunogenic pattern of malignant cells. Remarkably, several anticancer drugs impact both the abscopal effect and ICD. In addition, certain classes of anticancer agents are able to amplify already expressed tumor-associated antigens (TAA). More importantly, other drugs, especially triazenes, induce the appearance of new tumor neoantigens (TNA), a phenomenon that we termed drug-induced xenogenization (DIX). The adoption of the abscopal effect is proposed as a potential therapeutic modality when properly applied concomitantly with drug-induced increase in tumor cell immunogenicity and ICD. Although little to no preclinical or clinical studies are presently available on this subject, we discuss this issue in terms of potential mechanisms and therapeutic benefits. Upcoming investigations are aimed at evaluating how chemical anticancer drugs, radiation, and immunotherapies are interacting and cooperate in evoking the abscopal effect, tumor xenogenization and ICD, paving the way for new and possibly successful approaches in cancer therapy.
AbstractList The current state of cancer treatment is still far from being satisfactory considering the strong impairment of patients' quality of life and the high lethality of malignant diseases. Therefore, it is critical for innovative approaches to be tested in the near future. In view of the crucial role that is played by tumor immunity, the present review provides essential information on the immune-mediated effects potentially generated by the interplay between ionizing radiation and cytotoxic antitumor agents when interacting with target malignant cells. Therefore, the radiation-dependent abscopal effect (i.e., a biological effect of ionizing radiation that occurs outside the irradiated field), the influence of cancer chemotherapy on the antigenic pattern of target neoplastic cells, and the immunogenic cell death (ICD) caused by anticancer agents are the main topics of this presentation. It is widely accepted that tumor immunity plays a fundamental role in generating an abscopal effect and that anticancer drugs can profoundly influence not only the host immune responses, but also the immunogenic pattern of malignant cells. Remarkably, several anticancer drugs impact both the abscopal effect and ICD. In addition, certain classes of anticancer agents are able to amplify already expressed tumor-associated antigens (TAA). More importantly, other drugs, especially triazenes, induce the appearance of new tumor neoantigens (TNA), a phenomenon that we termed drug-induced xenogenization (DIX). The adoption of the abscopal effect is proposed as a potential therapeutic modality when properly applied concomitantly with drug-induced increase in tumor cell immunogenicity and ICD. Although little to no preclinical or clinical studies are presently available on this subject, we discuss this issue in terms of potential mechanisms and therapeutic benefits. Upcoming investigations are aimed at evaluating how chemical anticancer drugs, radiation, and immunotherapies are interacting and cooperate in evoking the abscopal effect, tumor xenogenization and ICD, paving the way for new and possibly successful approaches in cancer therapy.The current state of cancer treatment is still far from being satisfactory considering the strong impairment of patients' quality of life and the high lethality of malignant diseases. Therefore, it is critical for innovative approaches to be tested in the near future. In view of the crucial role that is played by tumor immunity, the present review provides essential information on the immune-mediated effects potentially generated by the interplay between ionizing radiation and cytotoxic antitumor agents when interacting with target malignant cells. Therefore, the radiation-dependent abscopal effect (i.e., a biological effect of ionizing radiation that occurs outside the irradiated field), the influence of cancer chemotherapy on the antigenic pattern of target neoplastic cells, and the immunogenic cell death (ICD) caused by anticancer agents are the main topics of this presentation. It is widely accepted that tumor immunity plays a fundamental role in generating an abscopal effect and that anticancer drugs can profoundly influence not only the host immune responses, but also the immunogenic pattern of malignant cells. Remarkably, several anticancer drugs impact both the abscopal effect and ICD. In addition, certain classes of anticancer agents are able to amplify already expressed tumor-associated antigens (TAA). More importantly, other drugs, especially triazenes, induce the appearance of new tumor neoantigens (TNA), a phenomenon that we termed drug-induced xenogenization (DIX). The adoption of the abscopal effect is proposed as a potential therapeutic modality when properly applied concomitantly with drug-induced increase in tumor cell immunogenicity and ICD. Although little to no preclinical or clinical studies are presently available on this subject, we discuss this issue in terms of potential mechanisms and therapeutic benefits. Upcoming investigations are aimed at evaluating how chemical anticancer drugs, radiation, and immunotherapies are interacting and cooperate in evoking the abscopal effect, tumor xenogenization and ICD, paving the way for new and possibly successful approaches in cancer therapy.
The current state of cancer treatment is still far from being satisfactory considering the strong impairment of patients’ quality of life and the high lethality of malignant diseases. Therefore, it is critical for innovative approaches to be tested in the near future. In view of the crucial role that is played by tumor immunity, the present review provides essential information on the immune-mediated effects potentially generated by the interplay between ionizing radiation and cytotoxic antitumor agents when interacting with target malignant cells. Therefore, the radiation-dependent abscopal effect (i.e., a biological effect of ionizing radiation that occurs outside the irradiated field), the influence of cancer chemotherapy on the antigenic pattern of target neoplastic cells, and the immunogenic cell death (ICD) caused by anticancer agents are the main topics of this presentation. It is widely accepted that tumor immunity plays a fundamental role in generating an abscopal effect and that anticancer drugs can profoundly influence not only the host immune responses, but also the immunogenic pattern of malignant cells. Remarkably, several anticancer drugs impact both the abscopal effect and ICD. In addition, certain classes of anticancer agents are able to amplify already expressed tumor-associated antigens (TAA). More importantly, other drugs, especially triazenes, induce the appearance of new tumor neoantigens (TNA), a phenomenon that we termed drug-induced xenogenization (DIX). The adoption of the abscopal effect is proposed as a potential therapeutic modality when properly applied concomitantly with drug-induced increase in tumor cell immunogenicity and ICD. Although little to no preclinical or clinical studies are presently available on this subject, we discuss this issue in terms of potential mechanisms and therapeutic benefits. Upcoming investigations are aimed at evaluating how chemical anticancer drugs, radiation, and immunotherapies are interacting and cooperate in evoking the abscopal effect, tumor xenogenization and ICD, paving the way for new and possibly successful approaches in cancer therapy.
Author Kaina, Bernd
Giuliani, Anna
Franzese, Ornella
Giannetti, Elisa
De Vecchis, Liana
Aquino, Angelo
Torino, Francesco
Cioccoloni, Giorgia
Fuggetta, Maria Pia
Faraoni, Isabella
Bonmassar, Enzo
AuthorAffiliation 4 Institute of Translational Pharmacology, Consiglio Nazionale delle Ricerche (CNR), Via Fosso del Cavaliere, 00133 Rome, Italy; mariapia.fuggetta@ift.cnr.it (M.P.F.); agiuliani37@yahoo.it (A.G.)
3 School of Food Science and Nutrition, University of Leeds, Leeds LS29JT, UK
5 Institute of Toxicology, University Medical Center, D-55131 Mainz, Germany
1 School of Medicine, Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; franzese@uniroma2.it (O.F.); g.cioccoloni@leeds.ac.uk (G.C.); angelo.aquino@uniroma2.it (A.A.); faraoni@med.uniroma2.it (I.F.); lianadev49@yahoo.com (L.D.V.)
2 Department of Systems Medicine, Medical Oncology, University of Rome Tor Vergata, 00133 Rome, Italy; torino@med.uniroma2.it (F.T.); elisag1611@gmail.com (E.G.)
AuthorAffiliation_xml – name: 5 Institute of Toxicology, University Medical Center, D-55131 Mainz, Germany
– name: 4 Institute of Translational Pharmacology, Consiglio Nazionale delle Ricerche (CNR), Via Fosso del Cavaliere, 00133 Rome, Italy; mariapia.fuggetta@ift.cnr.it (M.P.F.); agiuliani37@yahoo.it (A.G.)
– name: 3 School of Food Science and Nutrition, University of Leeds, Leeds LS29JT, UK
– name: 2 Department of Systems Medicine, Medical Oncology, University of Rome Tor Vergata, 00133 Rome, Italy; torino@med.uniroma2.it (F.T.); elisag1611@gmail.com (E.G.)
– name: 1 School of Medicine, Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; franzese@uniroma2.it (O.F.); g.cioccoloni@leeds.ac.uk (G.C.); angelo.aquino@uniroma2.it (A.A.); faraoni@med.uniroma2.it (I.F.); lianadev49@yahoo.com (L.D.V.)
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2021 by the authors. 2021
Copyright_xml – notice: 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/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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SubjectTerms Antigens
Brain cancer
Cancer therapies
Chemotherapy
Endocrine therapy
Immune response
Immunotherapy
Melanoma
Mutation
Radiation therapy
Review
Skin cancer
Tumors
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