Immunogenic Cell Death in Cancer and Infectious Disease

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (20 July 2022) | Viewed by 6420

Special Issue Editors


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Guest Editor
Cancer Center, China Medical University, Taichung 404, Taiwan
Interests: Radiation Oncology; Oncoimmunology; Cancer Treatment

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Co-Guest Editor
Translation Research Core, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan
Interests: cancer immunology; radiation oncology and cancer treatment

Special Issue Information

Dear Colleagues,

Immune checkpoint blockades have been demonstrated to benefit patients in different malignancies. However, only 20–30% of cancer patients show clinical responses to current immunotherapy. Combinational therapies with immunogenic chemotherapy/radiotherapy and immunotherapies have shown impressing clinical efficacy in preclinical studies and clinical trials. These immunogenic chemotherapies, radiotherapies and targeted therapies elicit immunogenic cell death (ICD) to release damage-associated molecular patterns (DAMPs), which can increase the anti-cancer immunity. The concept of ICD provides us with new strategies to increase the therapeutic effect of immunotherapies. Therefore, several studies have aimed to discover ICD inducers to boost anti-cancer immune responses by either increasing cancer immunogenicity or modulating the tumor microenvironment. In addition to the importance of ICD in anti-cancer immunity, several infectious pathogens have devised strategies to manipulate and limit the emission of DAMPs from dying cells, thereby avoiding immune recognition. The present Special Issue intends to contribute to the advancement of the field, accepting both comprehensive reviews and original research articles.

Prof. Dr. K.S. Clifford Chao
Dr. Kevin Chih-Yang Huang
Guest Editors

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Keywords

  • immunogenic cell death
  • radiotherapy
  • chemotherapy
  • anti-cancer immunity
  • immunotherapy
  • infectious disease

Published Papers (3 papers)

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Research

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22 pages, 825 KiB  
Article
Exploring the Interactions of Oncolytic Viral Therapy and Immunotherapy of Anti-CTLA-4 for Malignant Melanoma Mice Model
by Jui-Ling Yu, Sophia R.-J. Jang and Kwei-Yan Liu
Cells 2023, 12(3), 507; https://doi.org/10.3390/cells12030507 - 03 Feb 2023
Cited by 3 | Viewed by 2107
Abstract
Oncolytic ability to direct target and lyse tumor cells makes oncolytic virus therapy (OVT) a promising approach to treating cancer. Despite its therapeutic potential to stimulate anti-tumor immune responses, it also has immunosuppressive effects. The efficacy of OVTs as monotherapies can be enhanced [...] Read more.
Oncolytic ability to direct target and lyse tumor cells makes oncolytic virus therapy (OVT) a promising approach to treating cancer. Despite its therapeutic potential to stimulate anti-tumor immune responses, it also has immunosuppressive effects. The efficacy of OVTs as monotherapies can be enhanced by appropriate adjuvant therapy such as anti-CTLA-4. In this paper, we propose a mathematical model to explore the interactions of combined therapy of oncolytic viruses and a checkpoint inhibitor, anti-CTLA-4. The model incorporates both the susceptible and infected tumor populations, natural killer cell population, virus population, tumor-specific immune populations, virus-specific immune populations, tumor suppressive cytokine IFN-g, and the effect of immune checkpoint inhibitor CTLA-4. In particular, we distinguish the tumor-specific immune abilities of CD8+ T, NK cells, and CD4+ T cells and describe the destructive ability of cytokine on tumor cells as well as the inhibitory capacity of CTLA-4 on various components. Our model is validated through the experimental results. We also investigate various dosing strategies to improve treatment outcomes. Our study reveals that tumor killing rate by cytokines, cytokine decay rate, and tumor growth rate play important roles on both the OVT monotherapy and the combination therapy. Moreover, parameters related to CD8+ T cell killing have a large impact on treatment outcomes with OVT alone, whereas parameters associated with IFN-g strongly influence treatment responses for the combined therapy. We also found that virus killing by NK cells may halt the desired spread of OVs and enhance the probability of tumor escape during the treatment. Our study reveals that it is the activation of host anti-tumor immune system responses rather than its direct destruction of the tumor cells plays a major biological function of the combined therapy. Full article
(This article belongs to the Special Issue Immunogenic Cell Death in Cancer and Infectious Disease)
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15 pages, 5350 KiB  
Article
Upregulated Immunogenic Cell-Death-Associated Gene Signature Predicts Reduced Responsiveness to Immune-Checkpoint-Blockade Therapy and Poor Prognosis in High-Grade Gliomas
by Xin Tang, Dongfang Guo, Xi Yang, Rui Chen, Qingming Jiang, Zhen Zeng, Yu Li and Zhenyu Li
Cells 2022, 11(22), 3655; https://doi.org/10.3390/cells11223655 - 17 Nov 2022
Cited by 2 | Viewed by 1657
Abstract
Background: Immunogenic cell death (ICD) has emerged as a potential mechanism mediating adaptive immune response and tumor immunity in anti-cancer treatment. However, the signature of ICD in high-grade gliomas (HGGs) remains largely unknown, and its relevance to immunotherapies is still undetermined. The purpose [...] Read more.
Background: Immunogenic cell death (ICD) has emerged as a potential mechanism mediating adaptive immune response and tumor immunity in anti-cancer treatment. However, the signature of ICD in high-grade gliomas (HGGs) remains largely unknown, and its relevance to immunotherapies is still undetermined. The purpose of this study is to identify ICD-associated genotypes in order to explore their relevance to tumor immunity, patient prognosis and therapeutic efficacy of immune checkpoint blockade (ICB) therapy in HGGs. Methods: Bulk RNA-seq data and clinical information on 169 and 297 patients were obtained from the Cancer Genome Atlas (TCGA) and China Glioma Genome Atlas (CGGA), respectively. The functional enrichment and characterization of ICD genotyping were detected, and the ICD prognostic signature prediction model was constructed using least absolute shrinkage and selection operator (LASSO) regression. The responsiveness to immunotherapy was predicted according to the scoring of the ICD prognostic signature. Results: The HGG patients with high ICD gene signature (C1) showed poor outcomes, increased activity of immune modulation and immune escape, high levels of immune-checkpoint markers, and HLA-related genes, which may explain their reduced response to ICB immunotherapy. A gene set of the ICD signature, composing FOXP3, IL6 LY96, MYD88 and PDIA3, showed an independent prognostic value in both the TCGA and the CGGA HGG cohort. Conclusions: Our in silico analyses identified the ICD gene signature in HGGs with potential implications for predicting the responsiveness to ICB immune therapy and patient outcomes. Full article
(This article belongs to the Special Issue Immunogenic Cell Death in Cancer and Infectious Disease)
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11 pages, 2049 KiB  
Commentary
Cellular and Molecular Signaling as Targets for Cancer Vaccine Therapeutics
by Wen-Chi Wei, Lie-Fen Shyur and Ning-Sun Yang
Cells 2022, 11(9), 1590; https://doi.org/10.3390/cells11091590 - 09 May 2022
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Abstract
Plenty of evidence has recently shown that various inflammatory activities at the local tissue, organ, or even the whole body (systemic) level are strongly linked to many life-threatening chronic diseases, most notably various cancers. However, only very limited information is available for making [...] Read more.
Plenty of evidence has recently shown that various inflammatory activities at the local tissue, organ, or even the whole body (systemic) level are strongly linked to many life-threatening chronic diseases, most notably various cancers. However, only very limited information is available for making good use of our supporting immune-modulatory therapeutics for the treatment of cancers. This may result from a lack of studies on specific remedies for efficacious control or modulatory suppression of inflammation-related cancerous diseases. Our group and laboratories were fortunate to have initiated and consistently pursued an integrated team-work program project, aimed at investigating selected medicinal herbs and the derived, purified phytochemical compounds. We focused on the study of key and specific immune-signaling mechanisms at the cellular and molecular levels. We were fortunate to obtain a series of fruitful research results. We believe that our key findings reported herein may be helpful for proposing future thematic and integrated research projects that aim to develop future phytochemical drugs against cancers. The mechanisms of the cellular and molecular systems involved in inflammation are becoming increasingly recognized as keystones for the development of future therapeutic approaches for many chronic and cancerous diseases. Recently, the immune checkpoint inhibitors such as antibodies against PD-1 and/or PD-L1 have been shown to be too expensive for general clinical use, and their effects far from optimal, often showing little or no effect or only short-term efficacy. These results point to the need for developing future immune-regulatory or modulatory therapeutics. Full article
(This article belongs to the Special Issue Immunogenic Cell Death in Cancer and Infectious Disease)
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