scholarly journals Immunogenic Cell Death and Elimination of Immunosuppressive Cells: A Double-Edged Sword of Chemotherapy

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2637 ◽  
Author(s):  
Jean-David Fumet ◽  
Emeric Limagne ◽  
Marion Thibaudin ◽  
Francois Ghiringhelli
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Immune Escape ◽  
Adaptive Immune Response ◽  
Immunogenic Cell Death ◽  
Regulated Cell Death ◽  
Immunological Effects ◽  
Current Area ◽  
Immunosuppressive Cells ◽  
Main Effects

Chemotherapy is initially used to kill proliferative cells. In the current area of emerging immunotherapy, chemotherapies have shown their ability to modulate the tumor micro environment and immune response. We focus here on two main effects: first, immunogenic cell death, defined as a form of regulated cell death (RCD) that is sufficient to activate an adaptive immune response in immunocompetent hosts; and second, the depletion of suppressive cells, known to play a major role in immune escape and resistance to immunotherapy. In this review, we present a review of different classically used chemotherapies focusing on this double effect on immunity. These immunological effects of chemotherapy could be exploited to promote efficacy of immunotherapy. Broadening our understanding will make it possible to provide rationales for the combination of chemoimmunotherapy in early clinical trials.

scholarly journals Consensus guidelines for the definition, detection and interpretation of immunogenic cell death

2020 ◽  
Vol 8 (1) ◽  
pp. e000337 ◽  
Author(s):  
Lorenzo Galluzzi ◽  
Ilio Vitale ◽  
Sarah Warren ◽  
Sandy Adjemian ◽  
Patrizia Agostinis ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Adaptive Immune Response ◽  
Operational Definition ◽  
Immunogenic Cell Death ◽  
Adaptive Immune ◽  
Regulated Cell Death ◽  
Definition Of

Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.

scholarly journals An Immunogenic Cell Death-Related Classification Predicts Prognosis and Response to Immunotherapy in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Xinwen Wang ◽  
Shouwu Wu ◽  
Feng Liu ◽  
Dianshan Ke ◽  
Xinwu Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Clinical Outcomes ◽  
Immune Cell ◽  
Adaptive Immune Response ◽  
Immunogenic Cell Death ◽  
Consensus Clustering ◽  
Immune Microenvironment ◽  
Regulated Cell Death ◽  
Tumor Immune Microenvironment

Immunogenic cell death (ICD) has been classified as a form of regulated cell death (RCD) that is sufficient to activate an adaptive immune response. Accumulating evidence has demonstrated the ability of ICD to reshape the tumor immune microenvironment through the emission of danger signals or DAMPs, which may contribute to the immunotherapy. Currently, identification of ICD-associated biomarkers that stratify patients according to their benefit from ICD immunotherapy would be of great advantage. Here, we identified two ICD-associated subtypes by consensus clustering. ICD-high subtype was associated with the favorable clinical outcomes, abundant immune cell infiltration, and high activity of immune response signaling. Besides, we established and validated an ICD-related prognostic model that predicted the survival of HNSCC and was associated with tumor immune microenvironment. In conclusion, we established a new classification system of HNSCC based on ICD signatures. This stratification had significant clinical outcomes for estimating prognosis, as well as the immunotherapy of HNSCC patients

Rediscovery of Nanoparticle-based Therapeutics: Boosting Immunogenic Cell Death for Potential Application in Cancer Immunotherapy

2021 ◽  
Author(s):  
Suah Yang ◽  
In-Cheol Sun ◽  
Hee Sook Hwang ◽  
Man Kyu Shim ◽  
Hong Yeol Yoon ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Cancer Immunotherapy ◽  
Potential Application ◽  
Adaptive Immune Response ◽  
Immunogenic Cell Death ◽  
Living Body ◽  
Adaptive Immune ◽  
Physical Stimuli ◽  
Molecular Patterns

Immunogenic cell death (ICD) occurred by chemical and physical stimuli has shown the potential to activate an adaptive immune response in the immune-competent living body through releasing danger-associated molecular patterns...

scholarly journals Nano-Pulse Stimulation induces immunogenic cell death in human papillomavirus-transformed tumors and initiates an adaptive immune response

PLoS ONE ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. e0191311 ◽  
Author(s):  
Joseph G. Skeate ◽  
Diane M. Da Silva ◽  
Elena Chavez-Juan ◽  
Snjezana Anand ◽  
Richard Nuccitelli ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Human Papillomavirus ◽  
Adaptive Immune Response ◽  
Immunogenic Cell Death ◽  
Adaptive Immune ◽  
Pulse Stimulation

scholarly journals Damage-Associated Molecular Patterns Modulation by microRNA: Relevance on Immunogenic Cell Death and Cancer Treatment Outcome

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2566
Author(s):  
María Julia Lamberti ◽  
Annunziata Nigro ◽  
Vincenzo Casolaro ◽  
Natalia Belén Rumie Vittar ◽  
Jessica Dal Col
Keyword(s):  
Cell Death ◽  
Tumor Cells ◽  
Cell Activation ◽  
Adaptive Immune Response ◽  
Current Status ◽  
Immunogenic Cell Death ◽  
Basal Expression ◽  
Antigen Presenting ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Immunogenic cell death (ICD) in cancer is a functionally unique regulated form of stress-mediated cell death that activates both the innate and adaptive immune response against tumor cells. ICD makes dying cancer cells immunogenic by improving both antigenicity and adjuvanticity. The latter relies on the spatiotemporally coordinated release or exposure of danger signals (DAMPs) that drive robust antigen-presenting cell activation. The expression of DAMPs is often constitutive in tumor cells, but it is the initiating stressor, called ICD-inducer, which finally triggers the intracellular response that determines the kinetics and intensity of their release. However, the contribution of cell-autonomous features, such as the epigenetic background, to the development of ICD has not been addressed in sufficient depth. In this context, it has been revealed that several microRNAs (miRNAs), besides acting as tumor promoters or suppressors, can control the ICD-associated exposure of some DAMPs and their basal expression in cancer. Here, we provide a general overview of the dysregulation of cancer-associated miRNAs whose targets are DAMPs, through which new molecular mediators that underlie the immunogenicity of ICD were identified. The current status of miRNA-targeted therapeutics combined with ICD inducers is discussed. A solid comprehension of these processes will provide a framework to evaluate miRNA targets for cancer immunotherapy.

scholarly journals Calreticulin—Multifunctional Chaperone in Immunogenic Cell Death: Potential Significance as a Prognostic Biomarker in Ovarian Cancer Patients

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 130
Author(s):  
Michal Kielbik ◽  
Izabela Szulc-Kielbik ◽  
Magdalena Klink
Keyword(s):  
Ovarian Cancer ◽  
Cell Death ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Cytotoxic T Cells ◽  
Adaptive Immune Response ◽  
Ovarian Cancer Cells ◽  
Immunogenic Cell Death ◽  
Antigen Presenting ◽  
Molecular Patterns

Immunogenic cell death (ICD) is a type of death, which has the hallmarks of necroptosis and apoptosis, and is best characterized in malignant diseases. Chemotherapeutics, radiotherapy and photodynamic therapy induce intracellular stress response pathways in tumor cells, leading to a secretion of various factors belonging to a family of damage-associated molecular patterns molecules, capable of inducing the adaptive immune response. One of them is calreticulin (CRT), an endoplasmic reticulum-associated chaperone. Its presence on the surface of dying tumor cells serves as an “eat me” signal for antigen presenting cells (APC). Engulfment of tumor cells by APCs results in the presentation of tumor’s antigens to cytotoxic T-cells and production of cytokines/chemokines, which activate immune cells responsible for tumor cells killing. Thus, the development of ICD and the expression of CRT can help standard therapy to eradicate tumor cells. Here, we review the physiological functions of CRT and its involvement in the ICD appearance in malignant disease. Moreover, we also focus on the ability of various anti-cancer drugs to induce expression of surface CRT on ovarian cancer cells. The second aim of this work is to discuss and summarize the prognostic/predictive value of CRT in ovarian cancer patients.

scholarly journals Biomarkers of Radiotherapy-Induced Immunogenic Cell Death

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 930
Author(s):  
Rianne D. W. Vaes ◽  
Lizza E. L. Hendriks ◽  
Marc Vooijs ◽  
Dirk De Ruysscher
Keyword(s):  
Cell Death ◽  
Immune Responses ◽  
Tumor Cells ◽  
Immunogenic Cell Death ◽  
Type I ◽  
Future Studies ◽  
Regulated Cell Death ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Potential Biomarkers

Radiation therapy (RT) can induce an immunogenic variant of regulated cell death that can initiate clinically relevant tumor-targeting immune responses. Immunogenic cell death (ICD) is accompanied by the exposure and release of damage-associated molecular patterns (DAMPs), chemokine release, and stimulation of type I interferon (IFN-I) responses. In recent years, intensive research has unraveled major mechanistic aspects of RT-induced ICD and has resulted in the identification of immunogenic factors that are released by irradiated tumor cells. However, so far, only a limited number of studies have searched for potential biomarkers that can be used to predict if irradiated tumor cells undergo ICD that can elicit an effective immunogenic anti-tumor response. In this article, we summarize the available literature on potential biomarkers of RT-induced ICD that have been evaluated in cancer patients. Additionally, we discuss the clinical relevance of these findings and important aspects that should be considered in future studies.

scholarly journals Importance of the PD-1/PD-L1 Axis for Malignant Transformation and Risk Assessment of Oral Leukoplakia

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 194
Author(s):  
Jutta Ries ◽  
Abbas Agaimy ◽  
Falk Wehrhan ◽  
Christoph Baran ◽  
Stella Bolze ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Malignant Transformation ◽  
Immune Escape ◽  
Checkpoint Inhibitors ◽  
Precancerous Lesions ◽  
Death Receptor ◽  
Oral Leukoplakia ◽  
Significant Difference

Background: The programmed cell death ligand 1/programmed cell death receptor 1 (PD-L1/PD-1) Immune Checkpoint is an important modulator of the immune response. Overexpression of the receptor and its ligands is involved in immunosuppression and the failure of an immune response against tumor cells. PD-1/PD-L1 overexpression in oral squamous cell carcinoma (OSCC) compared to healthy oral mucosa (NOM) has already been demonstrated. However, little is known about its expression in oral precancerous lesions like oral leukoplakia (OLP). The aim of the study was to investigate whether an increased expression of PD-1/PD-L1 already exists in OLP and whether it is associated with malignant transformation. Material and Methods: PD-1 and PD-L1 expression was immunohistologically analyzed separately in the epithelium (E) and the subepithelium (S) of OLP that had undergone malignant transformation within 5 years (T-OLP), in OLP without malignant transformation (N-OLP), in corresponding OSCC and in NOM. Additionally, RT-qPCR analysis for PD-L1 expression was done in the entire tissues. Additionally, the association between overexpression and malignant transformation, dysplasia and inflammation were examined. Results: Compared to N-OLP, there were increased levels of PD-1 protein in the epithelial and subepithelial layers of T-OLP (pE = 0.001; pS = 0.005). There was no significant difference in PD-L1 mRNA expression between T-OLP and N-OLP (p = 0.128), but the fold-change increase between these groups was significant (Relative Quantification (RQ) = 3.1). In contrast to N-OLP, the PD-L1 protein levels were significantly increased in the epithelial layers of T-OLP (p = 0.007), but not in its subepithelial layers (p = 0.25). Importantly, increased PD-L1 levels were significantly associated to malignant transformation within 5 years. Conclusion: Increased levels of PD-1 and PD-L1 are related to malignant transformation in OLP and may represent a promising prognostic indicator to determine the risk of malignant progression of OLP. Increased PD-L1 levels might establish an immunosuppressive microenvironment, which could favor immune escape and thereby contribute to malignant transformation. Hence, checkpoint inhibitors could counteract tumor development in OLP and may serve as efficient therapeutic strategy in patients with high-risk precancerous lesions.

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