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Cancers
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Immunogenic Cell Death and Immunotherapy in Cancers
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Immunogenic Cell Death and Immunotherapy in Cancers

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 May 2021) | Viewed by 37150

Special Issue Editor

Prof. Dr. Alberto Anel

E-Mail Website
Guest Editor
Department of Biochemistry and Molecular and Cell Biology, University of Zaragoza, 50009 Zaragoza, Spain
Interests: apoptosis; cancer immunotherapy; NK cells; cytotoxic T lymphocytes; granulysin; Fas ligand; TRAIL

Special Issue Information

Dear Colleagues,

Over the past decade, immunotherapy has been demonstrated to have clinical efficacy in a wide variety of human tumours. However, not all patients show a positive and durable response to current immunotherapy regimens. Research is ongoing in alternative immunotherapies, such as those based in adoptive cell transfer, or in finding the right combination between chemotherapy/radiotherapy and immunotherapies. The concepts of immunogenic cell death (ICD) and danger signalling have provided us with new clues to understand these effects. Several screening studies have been carried out to discover bona fide ICD inducers that bring about in vivo anti-cancer immune responses. These positive interactions can be due to direct effects over cancer cell death immunogenicity, or to the modulation of the immune environment, and these aspects need further clarification. Finally, evidence relating gut microbiota to positive or negative immunotherapeutic responses is also growing. However, this subject needs further experimental authentication and definition, especially in clinical practice. The present Special Issue intends to contribute to the advancement of the field, accepting both reviews and original research articles.

Prof. Dr. Alberto Anel
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • immunogenic cell death
  • immunotherapy

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Published Papers (7 papers)

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Research

Jump to: Review

15 pages, 2747 KiB  
Article
Increased Immunogenicity of a Minimally Immunogenic Tumor after Cancer-Targeting Near Infrared Photoimmunotherapy
by Hiroaki Wakiyama, Aki Furusawa, Ryuhei Okada, Fuyuki Inagaki, Takuya Kato, Yasuhiro Maruoka, Peter L. Choyke and Hisataka Kobayashi
Cancers 2020, 12(12), 3747; https://doi.org/10.3390/cancers12123747 - 12 Dec 2020
Cited by 26 | Viewed by 3374
Abstract
Near-infrared photoimmunotherapy (NIR-PIT) is a highly selective cancer treatment that employs an antibody photoabsorber conjugate (APC) composed of a targeting monoclonal antibody (mAb) conjugated with a photoactivatable phthalocyanine-derivative dye. Once injected and allowed to bind to a tumor, the APC is activated by [...] Read more.
Near-infrared photoimmunotherapy (NIR-PIT) is a highly selective cancer treatment that employs an antibody photoabsorber conjugate (APC) composed of a targeting monoclonal antibody (mAb) conjugated with a photoactivatable phthalocyanine-derivative dye. Once injected and allowed to bind to a tumor, the APC is activated by local near-infrared light which kills cancer cells and induces a strong immune response in the tumor microenvironment by unmasking of new tumor antigens emerging from damaged tumor cells. Due to its ability to incite an immune reaction, even in poorly immunogenic tumors, NIR-PIT has the potential to enhance immunogenicity in tumors especially after immune checkpoint inhibition. In this study, we employ a poorly immunogenic MOC2-luc syngeneic tumor model and evaluate the efficacy of cancer-targeting CD44-targeted NIR-PIT. Increased infiltration of CD8+ T cells observed after NIR-PIT suggested an enhanced immune environment. Next, we evaluated tumor progression and survival after the combination of CD44-targeted NIR-PIT and short-term administration of an anti-PD1 immune checkpoint inhibitor (ICI) to further activate CD8+ T cells. Additionally, in mice in which the tumors were eradicated by this combination therapy, a re-challenge with fresh MOC2-luc cells demonstrated failure of tumor implantation implying acquired long-term immunity against the cancer cells. Combination therapy decreased tumor progression and prolonged survival significantly. Therefore, we concluded that NIR-PIT was able to convert a minimally immunogenic tumor unresponsive to anti-PD-1 ICI into a highly immunogenic tumor responsive to anti-PD-1 ICI, and this therapy was capable of inducing long-term immunity against the treated cancer. Full article
(This article belongs to the Special Issue Immunogenic Cell Death and Immunotherapy in Cancers)
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14 pages, 2435 KiB  
Article
Rafoxanide Induces Immunogenic Death of Colorectal Cancer Cells
by Antonio Di Grazia, Federica Laudisi, Davide Di Fusco, Eleonora Franzè, Angela Ortenzi, Ivan Monteleone, Giovanni Monteleone and Carmine Stolfi
Cancers 2020, 12(5), 1314; https://doi.org/10.3390/cancers12051314 - 21 May 2020
Cited by 17 | Viewed by 3713
Abstract
Colorectal cancer (CRC) is a major cause of cancer-related death in the world. Emerging evidence suggests that the clinical success of conventional chemotherapy does not merely rely on cell toxicity, but also results from the restoration of tumor immune surveillance. Anti-tumor immune response [...] Read more.
Colorectal cancer (CRC) is a major cause of cancer-related death in the world. Emerging evidence suggests that the clinical success of conventional chemotherapy does not merely rely on cell toxicity, but also results from the restoration of tumor immune surveillance. Anti-tumor immune response can be primed by immunogenic cell death (ICD), a form of apoptosis associated with endoplasmic reticulum stress (ERS) induction and the expression/release of specific damage-associated molecular patterns (DAMPs). Unfortunately, a limited number of ICD inducers have been identified so far. The anti-helmintic drug rafoxanide has recently showed anti-tumor activity in different cancer types, including CRC. As such latter effects relied on ERS activation, we here investigated whether rafoxanide could promote ICD of CRC cells. The potential of rafoxanide to induce ICD-related DAMPs in both human and mouse CRC cells was assessed by flow-cytometry, chemiluminescent assay and ELISA. In addition, the immunogenic potential of rafoxanide was assessed in vivo using a vaccination assay. Rafoxanide induced all the main DAMPs (ecto-calreticulin exposure, adenosine triphosphate (ATP)/high mobility group box 1 (HMGB1) release) required for ICD. We observed a marked increase of tumor-free survival among immunocompetent mice immunized with rafoxanide-treated dying tumor cells as compared with sham. Altogether, our data indicate rafoxanide as a bona fide ICD inducer. Full article
(This article belongs to the Special Issue Immunogenic Cell Death and Immunotherapy in Cancers)
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Review

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27 pages, 1047 KiB  
Review
Immunotherapy in Glioblastoma: A Clinical Perspective
by Nicolas Desbaillets and Andreas Felix Hottinger
Cancers 2021, 13(15), 3721; https://doi.org/10.3390/cancers13153721 - 24 Jul 2021
Cited by 18 | Viewed by 4167
Abstract
Glioblastoma is the most frequent and the most aggressive brain tumor. It is notoriously resistant to current treatments, and the prognosis remains dismal. Immunotherapies have revolutionized the treatment of numerous cancer types and generate great hope for glioblastoma, alas without success until now. [...] Read more.
Glioblastoma is the most frequent and the most aggressive brain tumor. It is notoriously resistant to current treatments, and the prognosis remains dismal. Immunotherapies have revolutionized the treatment of numerous cancer types and generate great hope for glioblastoma, alas without success until now. In this review, the rationale underlying immune targeting of glioblastoma, as well as the challenges faced when targeting these highly immunosuppressive tumors, are discussed. Innovative immune-targeting strategies including cancer vaccines, oncolytic viruses, checkpoint blockade inhibitors, adoptive cell transfer, and CAR T cells that have been investigated in glioblastoma are reviewed. From a clinical perspective, key clinical trial findings and ongoing trials are discussed for each approach. Finally, limitations, either biological or arising from trial designs are analyzed, and strategies to overcome them are presented. Proof of efficacy for immunotherapy approaches remains to be demonstrated in glioblastoma, but our rapidly expanding understanding of its biology, its immune microenvironment, and the emergence of novel promising combinatorial approaches might allow researchers to finally fulfill the medical need for GBM patients. Full article
(This article belongs to the Special Issue Immunogenic Cell Death and Immunotherapy in Cancers)
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30 pages, 3237 KiB  
Review
Restoring the Immunity in the Tumor Microenvironment: Insights into Immunogenic Cell Death in Onco-Therapies
by Ángela-Patricia Hernández, Pablo Juanes-Velasco, Alicia Landeira-Viñuela, Halin Bareke, Enrique Montalvillo, Rafael Góngora and Manuel Fuentes
Cancers 2021, 13(11), 2821; https://doi.org/10.3390/cancers13112821 - 5 Jun 2021
Cited by 34 | Viewed by 5898
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) [...] Read more.
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. Full article
(This article belongs to the Special Issue Immunogenic Cell Death and Immunotherapy in Cancers)
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19 pages, 1492 KiB  
Review
Enhance the Immune Checkpoint Inhibitors Efficacy with Radiotherapy Induced Immunogenic Cell Death: A Comprehensive Review and Latest Developments
by Adrien Procureur, Audrey Simonaggio, Jean-Emmanuel Bibault, Stéphane Oudard and Yann-Alexandre Vano
Cancers 2021, 13(4), 678; https://doi.org/10.3390/cancers13040678 - 8 Feb 2021
Cited by 37 | Viewed by 4002
Abstract
The immunogenic cell death (ICD) is defined as a regulated cell death able to induce an adaptive immunity. It depends on different parameters including sufficient antigenicity, adjuvanticity and favorable microenvironment conditions. Radiation therapy (RT), a pillar of modern cancer treatment, is being used [...] Read more.
The immunogenic cell death (ICD) is defined as a regulated cell death able to induce an adaptive immunity. It depends on different parameters including sufficient antigenicity, adjuvanticity and favorable microenvironment conditions. Radiation therapy (RT), a pillar of modern cancer treatment, is being used in many tumor types in curative, (neo) adjuvant, as well as metastatic settings. The anti-tumor effects of RT have been traditionally attributed to the mitotic cell death resulting from the DNA damages triggered by the release of reactive oxygen species. Recent evidence suggests that RT may also exert its anti-tumor effect by recruiting tumor-specific immunity. RT is able to induce the release of tumor antigens, to act as an immune adjuvant and thus to synergize with the anti-tumor immunity. The advent of new efficient immunotherapeutic agents, such as immune checkpoint inhibitors (ICI), in multiple tumor types sheds new light on the opportunity of combining RT and ICI. Here, we will describe the biological and radiobiological rationale of the RT-induced ICD. We will then focus on the interest to combine RT and ICI, from bench to bedside, and summarize the clinical data existing with this combination. Finally, RT technical adaptations to optimize the ICD induction will be discussed. Full article
(This article belongs to the Special Issue Immunogenic Cell Death and Immunotherapy in Cancers)
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25 pages, 1149 KiB  
Review
Challenges in Combining Immunotherapy with Radiotherapy in Recurrent/Metastatic Head and Neck Cancer
by Gaber Plavc, Tanja Jesenko, Miha Oražem and Primož Strojan
Cancers 2020, 12(11), 3197; https://doi.org/10.3390/cancers12113197 - 30 Oct 2020
Cited by 19 | Viewed by 4617
Abstract
Immunotherapy with immune checkpoint inhibitors (ICI) has recently become a standard part of the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), although the response rates are low. Numerous preclinical and clinical studies have now illuminated several mechanisms [...] Read more.
Immunotherapy with immune checkpoint inhibitors (ICI) has recently become a standard part of the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), although the response rates are low. Numerous preclinical and clinical studies have now illuminated several mechanisms by which radiotherapy (RT) enhances the effect of ICI. From RT-induced immunogenic cancer cell death to its effect on the tumor microenvironment and vasculature, the involved mechanisms are diverse and intertwined. Moreover, the research of these interactions is challenging because of the thin line between immunostimulatory and the immunosuppressive effect of RT. In the era of active research of immunoradiotherapy combinations, the significance of treatment and host-related factors that were previously seen as being less important is being revealed. The impact of dose and fractionation of RT is now well established, whereas selection of the number and location of the lesions to be irradiated in a multi-metastatic setting is something that is only now beginning to be understood. In addition to spatial factors, the timing of irradiation is as equally important and is heavily dependent on the type of ICI used. Interestingly, using smaller-than-conventional RT fields or even partial tumor volume RT could be beneficial in this setting. Among host-related factors, the role of the microbiome on immunotherapy efficacy must not be overlooked nor can we neglect the role of gut irradiation in a combined RT and ICI setting. In this review we elaborate on synergistic mechanisms of immunoradiotherapy combinations, in addition to important factors to consider in future immunoradiotherapy trial designs in R/M HNSCC. Full article
(This article belongs to the Special Issue Immunogenic Cell Death and Immunotherapy in Cancers)
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38 pages, 1760 KiB  
Review
Current Approaches for Combination Therapy of Cancer: The Role of Immunogenic Cell Death
by Zahra Asadzadeh, Elham Safarzadeh, Sahar Safaei, Ali Baradaran, Ali Mohammadi, Khalil Hajiasgharzadeh, Afshin Derakhshani, Antonella Argentiero, Nicola Silvestris and Behzad Baradaran
Cancers 2020, 12(4), 1047; https://doi.org/10.3390/cancers12041047 - 23 Apr 2020
Cited by 164 | Viewed by 10172
Abstract
Cell death resistance is a key feature of tumor cells. One of the main anticancer therapies is increasing the susceptibility of cells to death. Cancer cells have developed a capability of tumor immune escape. Hence, restoring the immunogenicity of cancer cells can be [...] Read more.
Cell death resistance is a key feature of tumor cells. One of the main anticancer therapies is increasing the susceptibility of cells to death. Cancer cells have developed a capability of tumor immune escape. Hence, restoring the immunogenicity of cancer cells can be suggested as an effective approach against cancer. Accumulating evidence proposes that several anticancer agents provoke the release of danger-associated molecular patterns (DAMPs) that are determinants of immunogenicity and stimulate immunogenic cell death (ICD). It has been suggested that ICD inducers are two different types according to their various activities. Here, we review the well-characterized DAMPs and focus on the different types of ICD inducers and recent combination therapies that can augment the immunogenicity of cancer cells. Full article
(This article belongs to the Special Issue Immunogenic Cell Death and Immunotherapy in Cancers)
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