Tumor Microenvironment-Triggered In-Situ Cancer Vaccines with Dual Immunogenic Cell Death Inductions for Elevated Antitumor and Antimetastatic Therapy

Certain cancer therapy has been shown to induce immunogenic cell death in cancer cells and may promote tumor progression instead. The external stress or stimuli may induce cell death and contribute toward the secretion of pro inflammatory molecules. The release of damage-associated molecular patterns (DAMPs) upon induction of therapy or cell death has been shown to induce an inflammatory response. Nevertheless, the mechanism as to how the DAMPs are released and engage in such activity needs further in-depth investigation. Interestingly, some studies have shown that DAMPs can be released through extracellular vesicles (EVs) and can bind to receptors such as toll-like receptors (TCRs). Ample pre-clinical studies have shown that cancer-derived EVs are able to modulate immune responses within the tumor microenvironment. However, the information on the presence of such DAMPs within EVs is still elusive. Therefore, this mini-review attempts to summarize and appraise studies that have shown the presence of DAMPs within cancer-EVs and how it affects the downstream cellular process.

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Pyroptotic and Necroptotic Cell Death in the Tumor Microenvironment and Their Potential to Stimulate Anti-Tumor Immune Responses

Frontiers in Oncology ◽

10.3389/fonc.2021.731598 ◽

2021 ◽

Vol 11 ◽

Author(s):

Allan Scarpitta ◽

Ulrich T. Hacker ◽

Hildegard Büning ◽

Olivier Boyer ◽

Sahil Adriouch

Keyword(s):

Cell Death ◽

Tumor Microenvironment ◽

Immune Responses ◽

Immune Cells ◽

Immunogenic Cell Death ◽

Chemotherapeutic Drugs ◽

Immune Functions ◽

Molecular Patterns ◽

Dying Cells ◽

Damage Associated Molecular Patterns

Cancer remains the second most common cause of death worldwide affecting around 10 million patients every year. Among the therapeutic options, chemotherapeutic drugs are widely used but often associated with side effects. In addition, toxicity against immune cells may hamper anti-tumor immune responses. Some chemotherapeutic drugs, however, preserve immune functions and some can even stimulate anti-tumor immune responses through the induction of immunogenic cell death (ICD) rather than apoptosis. ICD stimulates the immune system by several mechanisms including the release of damage-associated molecular patterns (DAMPs) from dying cells. In this review, we will discuss the consequences of inducing two recently characterized forms of ICD, i.e., pyroptosis and necroptosis, in the tumor microenvironment (TME) and the perspectives they may offer to increase the immunogenicity of the so-called cold tumors and to stimulate effective anti-tumor immune responses.

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Localized cocktail chemoimmunotherapy after in situ gelation to trigger robust systemic antitumor immune responses

Science Advances ◽

10.1126/sciadv.aaz4204 ◽

2020 ◽

Vol 6 (10) ◽

pp. eaaz4204 ◽

Cited By ~ 11

Author(s):

Yu Chao ◽

Chao Liang ◽

Huiquan Tao ◽

Yaran Du ◽

Di Wu ◽

...

Keyword(s):

Cell Death ◽

Immune Responses ◽

Cancer Recurrence ◽

Immune Checkpoint Blockade ◽

Systemic Toxicity ◽

Immunogenic Cell Death ◽

In Situ Gelation ◽

Immune Adjuvants ◽

Immune Adjuvant

Currently, there is a huge demand to develop chemoimmunotherapy with reduced systemic toxicity and potent efficacy to combat late-stage cancers with spreading metastases. Here, we report several “cocktail” therapeutic formulations by mixing immunogenic cell death (ICD)–inducing chemotherapeutics and immune adjuvants together with alginate (ALG) for localized chemoimmunotherapy. Immune checkpoint blockade (ICB) antibody may be either included into this cocktail for local injection or used via conventional intravenous injection. After injection of such cocktail into a solid tumor, in-situ gelation of ALG would lead to local retention and sustained release of therapeutics to reduce systemic toxicity. The chemotherapy-induced ICD with the help of immune adjuvant would trigger tumor-specific immune responses, which are further amplified by ICB to elicit potent systemic antitumor immune responses in destructing local tumors, eliminating metastases and inhibiting cancer recurrence. Our strategy of combining clinically used agents for tumor-localized cocktail chemoimmunotherapy possesses great potential for clinical translation.

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A cell membrane vehicle co-delivering sorafenib and doxorubicin remodel the tumor microenvironment and enhance immunotherapy by inducing immunogenic cell death in lung cancer cells

Journal of Materials Chemistry B ◽

10.1039/d0tb01052a ◽

2020 ◽

Vol 8 (34) ◽

pp. 7755-7765 ◽

Cited By ~ 1

Author(s):

Jun Wan ◽

Jian Wang ◽

Min Zhou ◽

Zhanpeng Rao ◽

Xiean Ling

Keyword(s):

Lung Cancer ◽

Cell Death ◽

Tumor Microenvironment ◽

Cancer Therapy ◽

Cell Membrane ◽

Cancer Cells ◽

Cancer Immunotherapy ◽

Lung Cancer Cells ◽

Immunogenic Cell Death ◽

A Cell

Cancer immunotherapy is a promising approach for cancer therapy but is usually hindered by the inhibition of the tumor microenvironment (TME).

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Immunogenic Cell Death-Based Cancer Vaccines

Frontiers in Immunology ◽

10.3389/fimmu.2021.697964 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ming-Zhu Jin ◽

Xi-Peng Wang

Keyword(s):

Cell Death ◽

Cancer Cells ◽

Cancer Immunotherapy ◽

Adaptive Immunity ◽

Cancer Vaccines ◽

Antitumor Immunity ◽

Immunogenic Cell Death ◽

Cancer Vaccination ◽

The Past ◽

Molecular Patterns

Cancer immunotherapy has achieved great advancement in the past decades. Whereas, its response is largely limited in immunologically cold tumors, in an urgent need to be solve. In recent years, an increasing number of studies have shown that inducing immunogenic cell deaths (ICDs) is an attractive approach to activate antitumor immunity. Upon specific stress, cancer cells undergo ICDs and dying cancer cells release danger associated molecular patterns (DAMPs), produce neoantigens and trigger adaptive immunity. ICDs exert a cancer vaccine-like effect and Inducement of ICDs mimics process of cancer vaccination. In this review, we propose a concept of ICD-based cancer vaccines and summarize sources of ICD-based cancer vaccines and their challenges, which may broaden the understandings of ICD and cancer vaccines in cancer immunotherapy.

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Combination Cancer Immunotherapy: Immunogenic Cell Death Inducing Fluorinated Mitochondria‐Disrupting Helical Polypeptide Synergizes with PD‐L1 Immune Checkpoint Blockade (Adv. Sci. 7/2021)

Advanced Science ◽

10.1002/advs.202170038 ◽

2021 ◽

Vol 8 (7) ◽

pp. 2170038

Author(s):

Seong Dong Jeong ◽

Bo‐Kyeong Jung ◽

Hyo Min Ahn ◽

DaeYong Lee ◽

JongHoon Ha ◽

...

Keyword(s):

Cell Death ◽

Cancer Immunotherapy ◽

Immune Checkpoint ◽

Immune Checkpoint Blockade ◽

Checkpoint Blockade ◽

Immunogenic Cell Death

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Biomarkers of Radiotherapy-Induced Immunogenic Cell Death

Cells ◽

10.3390/cells10040930 ◽

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.

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Combining PD-L1 Inhibitors with Immunogenic Cell Death Triggered by Chemo-Photothermal therapy via a Thermosensitive Liposome System to Stimulate Tumor-specific Immunological Response

Nanoscale ◽

10.1039/d1nr03288g ◽

2021 ◽

Author(s):

Jie Yu ◽

Xidong He ◽

Zigui Wang ◽

Yu Peng Wang ◽

Sha Liu ◽

...

Keyword(s):

Cell Death ◽

Immune Responses ◽

Photothermal Therapy ◽

Immunological Response ◽

Immune Checkpoint Blockade ◽

Immunogenic Cell Death ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Thermosensitive Liposome ◽

Liposome System

Immune checkpoint blockade (ICB) therapy in combination with immunogenic death (ICD) triggered by photothermal therapy (PTT) and oxaliplatin (OXA) treatment was expected to elicit both innate and adaptive immune responses...

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