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Immunogenic Cell Death, Immunogenic Surrender and Antitumor Immunity

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (10 July 2023) | Viewed by 14068

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Special Issue Editors

Dr. Yong Teng

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Guest Editor

Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA
Interests: metastasis; molecular pathway; cancer models; metabolism; tumor microenvironment; drug screening and development
Special Issues, Collections and Topics in MDPI journals

Dr. Zhi-Chun Ding

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Guest Editor

Georgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
Interests: cancer immunology; adoptive T cell therapy; cancer biology; T cell biology; innate immunity; chemotherapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Immunogenic cell death (ICD) and immunogenic surrender (IS) play vital roles in reversing dysfunctional antitumor immunity. It is argued that ICD and IS are two related but distinct immune surveillance mechanisms. ICD (e.g., pyroptosis) senses cell death associated with the exposure and release of numerous DAMPs, favoring the recruitment and maturation of antigen-presenting cells (APCs) to activate tumor-antigen-specific T cells. Meanwhile, IS senses the abnormal growth of cells, which is initiated by BoxA-mediated internalization of CD47 and the inhibition of tumor-cell proliferation. Growing evidence has unraveled many novel modalities with the ability to induce ICD and IS. However, we are still far from fully understanding the complexity of therapy-induced immunogenicity. With the advent of new information, technologies, and methodologies, it is time to delineate the significance and enigmatic mechanisms relevant to the ICD and/or IS in response to chemotherapy, radiotherapy, and targeted anticancer agents. This scientific evidence and these provocative ideas are essential to effectively translating science into practice. Therefore, we kindly invite you to contribute to this Special Issue with original research articles or comprehensive reviews on all aspects related to immunogenic cell death, immunogenic surrender, and antitumor immunity. This Special Issue is being initiated to increase our understanding of concepts and molecular mechanisms relevant to the antitumor effects of ICD and IS, and possibly to identify optimal therapeutic combinations for clinical cancer management.

Dr. Yong Teng
Dr. Zhi-Chun Ding
Guest Editors

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Keywords

cancer immunoediting signaling pathway
molecular mechanisms of immune surveillance
regulation of immunogenic cell death
regulation of immunogenic surrender
strategies to improve tumor immunogenicity
strategies to enhance antitumor immunity

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Published Papers (4 papers)

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Research

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10 pages, 1054 KiB

Open AccessArticle

Serum Amyloid A in Stable Patients with Chronic Obstructive Pulmonary Disease Does Not Reflect the Clinical Course of the Disease

by Marta Maskey-Warzęchowska, Renata Rubinsztajn, Tadeusz Przybyłowski, Krzysztof Karwat, Patrycja Nejman-Gryz, Magdalena Paplińska-Goryca and Ryszarda Chazan

Int. J. Mol. Sci. 2023, 24(3), 2478; https://doi.org/10.3390/ijms24032478 - 27 Jan 2023

Cited by 1 | Viewed by 1458

Abstract

Serum amyloid A (SAA) is a good systemic marker of the exacerbations of chronic obstructive pulmonary disease (COPD), but the significance of SAA in stable patients with COPD has not been widely investigated. We aimed to evaluate the SAA level in peripheral blood from stable patients with COPD and to search for correlations between SAA and other inflammatory markers and clinical characteristics of the disease. Serum SAA, IL-6, IL-8, TNF-alpha, basic blood investigations, pulmonary function testing and a 6-min walk test were performed. The correlations between SAA and other inflammatory markers, functional performance and the number of disease exacerbations were evaluated. A total of 100 consecutive patients with COPD were analyzed. No correlations between SAA and inflammatory markers as well as pulmonary function were found. Hierarchical clustering identified two clusters incorporating SAA: one comprised SAA, PaO₂ and FEV₁ and the second was formed of SAA and nine other disease markers. The SAA level was higher in patients with blood eosinophils < 2% when compared to those with blood eosinophils ≥ 2% (41.8 (19.5–69.7) ng/mL vs. 18.9 (1.0–54.5) ng/mL, respectively, p = 0.04). We conclude that, in combination with other important disease features, SAA may be useful for patient evaluation in stable COPD. Full article

(This article belongs to the Special Issue Immunogenic Cell Death, Immunogenic Surrender and Antitumor Immunity)

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15 pages, 3275 KiB

Open AccessArticle

Tumor Treating Fields (TTFields) Concomitant with Immune Checkpoint Inhibitors Are Therapeutically Effective in Non-Small Cell Lung Cancer (NSCLC) In Vivo Model

by Yiftah Barsheshet, Tali Voloshin, Boris Brant, Gadi Cohen, Lilach Koren, Roni Blatt, Shay Cahal, Tharwat Haj Khalil, Efrat Zemer Tov, Rom Paz, Anat Klein-Goldberg, Catherine Tempel-Brami, Sara Jacobovitch, Alexandra Volodin, Tal Kan, Bella Koltun, Cfir David, Adi Haber, Moshe Giladi, Uri Weinberg and Yoram Palti Show full author list Hide full author list

Int. J. Mol. Sci. 2022, 23(22), 14073; https://doi.org/10.3390/ijms232214073 - 15 Nov 2022

Cited by 16 | Viewed by 4896

Abstract

Tumor Treating Fields (TTFields) are electric fields that exert physical forces to disrupt cellular processes critical for cancer cell viability and tumor progression. TTFields induce anti-mitotic effects through the disruption of the mitotic spindle and abnormal chromosome segregation, which trigger several forms of cell death, including immunogenic cell death (ICD). The efficacy of TTFields concomitant with anti-programmed death-1 (anti-PD-1) treatment was previously shown in vivo and is currently under clinical investigation. Here, the potential of TTFields concomitant with anti- PD-1/anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) or anti-programmed death-ligand 1 (anti-PD-L1) immune checkpoint inhibitors (ICI) to improve therapeutic efficacy was examined in lung tumor-bearing mice. Increased circulating levels of high mobility group box 1 protein (HMGB1) and elevated intratumoral levels of phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α) were found in the TTFields-treated mice, indicative of ICD induction. The concomitant application of TTFields and ICI led to a significant decrease in tumor volume as compared to all other groups. In addition, significant increases in the number of tumor-infiltrating immune cells, specifically cytotoxic T-cells, were observed in the TTFields plus anti-PD-1/anti-CTLA-4 or anti-PD-L1 groups. Correspondingly, cytotoxic T-cells isolated from these tumors showed higher levels of IFN-γ production. Collectively, these results suggest that TTFields have an immunoactivating role that may be leveraged for concomitant treatment with ICI to achieve better tumor control by enhancing antitumor immunity. Full article

(This article belongs to the Special Issue Immunogenic Cell Death, Immunogenic Surrender and Antitumor Immunity)

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12 pages, 2931 KiB

Open AccessArticle

Calcium-Based Antimicrobial Peptide Compounds Attenuate DNFB-Induced Atopic Dermatitis-Like Skin Lesions via Th-Cells in BALB/c Mice

by Qingfeng Liu, Mengmeng Li, Na Wang, Chun He, Xian Jiang and Jingyi Li

Int. J. Mol. Sci. 2022, 23(19), 11371; https://doi.org/10.3390/ijms231911371 - 26 Sep 2022

Cited by 4 | Viewed by 2474

Abstract

Atopic dermatitis (AD) is a chronic and recurrent inflammatory skin disease, characterized by severe itching and recurrent skin lesions. We hypothesized that a novel treatment involving calcium-based antimicrobial peptide compounds (CAPCS), a combination of natural calcium extracted from marine shellfish, and a variety of antimicrobial peptides, may be beneficial for AD. We established a dinitrofluorobenzene (DNFB)-induced AD model in BALB/c mice to test our hypothesis. We observed mouse behavior and conducted histopathological and immunohistochemical analyses on skin lesions before and after CAPCS treatment. We also characterized the changes in the levels of cytokines, inflammatory mediators, and Toll-like receptors (TLRs) in plasma and skin lesions. The results showed that (i) topical application of CAPCS ameliorated AD-like skin lesions and reduced scratching behavior in BALB/c mice; (ii) CAPCS suppressed infiltration of inflammatory cells and inhibited the expression of inflammatory cytokines in AD-like skin lesions; (iii) CAPCS reduced plasma levels of inflammatory cytokines; and (iv) CAPCS inhibited TLR2 and TLR4 protein expression in skin lesions. Topical application of CAPCS exhibits a therapeutic effect on AD by inhibiting inflammatory immune responses via recruiting helper T cells and engaging the TLR2 and TLR4 signaling pathways. Therefore, CAPCS may be useful for the treatment of AD. Full article

(This article belongs to the Special Issue Immunogenic Cell Death, Immunogenic Surrender and Antitumor Immunity)

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Review

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19 pages, 17391 KiB

Open AccessReview

Single-Cell Analysis in Immuno-Oncology

by Maria-Ioanna Christodoulou and Apostolos Zaravinos

Int. J. Mol. Sci. 2023, 24(9), 8422; https://doi.org/10.3390/ijms24098422 - 8 May 2023

Cited by 13 | Viewed by 4400

Abstract

The complexity of the cellular and non-cellular milieu surrounding human tumors plays a decisive role in the course and outcome of disease. The high variability in the distribution of the immune and non-immune compartments within the tumor microenvironments (TME) among different patients governs the mode of their response or resistance to current immunotherapeutic approaches. Through deciphering this diversity, one can tailor patients’ management to meet an individual’s needs. Single-cell (sc) omics technologies have given a great boost towards this direction. This review gathers recent data about how multi-omics profiling, including the utilization of single-cell RNA sequencing (scRNA-seq), assay for transposase-accessible chromatin with sequencing (scATAC-seq), T-cell receptor sequencing (scTCR-seq), mass, tissue-based, or microfluidics cytometry, and related bioinformatics tools, contributes to the high-throughput assessment of a large number of analytes at single-cell resolution. Unravelling the exact TCR clonotype of the infiltrating T cells or pinpointing the classical or novel immune checkpoints across various cell subsets of the TME provide a boost to our comprehension of adaptive immune responses, their antigen specificity and dynamics, and grant suggestions for possible therapeutic targets. Future steps are expected to merge high-dimensional data with tissue localization data, which can serve the investigation of novel multi-modal biomarkers for the selection and/or monitoring of the optimal treatment from the current anti-cancer immunotherapeutic armamentarium. Full article

(This article belongs to the Special Issue Immunogenic Cell Death, Immunogenic Surrender and Antitumor Immunity)

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