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The Achilles' heel of cancer: targeting tumors via lysosome-induced immunogenic cell death.

ABSTRACT: Interest in the lysosome's potential role in anticancer therapies has recently been appreciated in the field of immuno-oncology. Targeting lysosomes triggers apoptotic pathways, inhibits cytoprotective autophagy, and activates a unique form of apoptosis known as immunogenic cell death (ICD). This mechanism stimulates a local and systemic immune response against dead-cell antigens. Stressors that can lead to ICD include an abundance of ROS which induce lysosome membrane permeability (LMP). Dying cells express markers that activate immune cells. Dendritic cells engulf the dying cell and then present the cell's neoantigens to T cells. The discovery of ICD-inducing agents is important due to their potential to trigger autoimmunity. In this review, we discuss the various mechanisms of activating lysosome-induced cell death in cancer cells specifically and the strategies that current laboratories are using to selectively promote LMP in tumors.

SUBMITTER: Iulianna T

PROVIDER: S-EPMC9151667 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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The Achilles' heel of cancer: targeting tumors via lysosome-induced immunogenic cell death.

Iulianna Taritsa T Kuldeep Neote N Eric Fossel F

Cell death & disease 20220530 5

Interest in the lysosome's potential role in anticancer therapies has recently been appreciated in the field of immuno-oncology. Targeting lysosomes triggers apoptotic pathways, inhibits cytoprotective autophagy, and activates a unique form of apoptosis known as immunogenic cell death (ICD). This mechanism stimulates a local and systemic immune response against dead-cell antigens. Stressors that can lead to ICD include an abundance of ROS which induce lysosome membrane permeability (LMP). Dying ...[more]

PMID: 35637197

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Project description:Emerging evidence has demonstrated that radiotherapy (RT) can not only cause direct damage to cancer cells but also lead to immunogenic cell death (ICD), which involves the activation of host antitumor immune response in tumor immune microenvironment (TIME). RT-induced ICD comprises the release of damage-associated molecular patterns (DAMPs) from dying cancer cells that result in the activation of tumor-specific immunity to elicit long-term antitumor efficacy in both original and abscopal tumor sites. Adenosine triphosphate (ATP), as an important DAMP released by irradiated cancer cells and an essential factor within purinergic pathway, can be further hydrolyzed to adenosine (ADO) by two key ectonucleotidases, CD39 and CD73, to further modulate the antitumor immunity in TIME through purinergic signaling via the interaction to its specific receptors such as adenosine 2A receptor (A2AR) and A2BR widely expressed on the surface of the components in TIME, including cancer cells and many immune effector cells. In this review, we first introduced key components in purinergic pathway including ATP, ADO, their receptors, and essential ectonucleotidases. Then we reviewed the regulation of ATP and ADO levels and their main mechanisms by which they promote tumor growth and broadly suppress antitumor immunity through inhibiting the pro-inflammatory response of dendritic cells, cytotoxic T lymphocytes, and natural killer cells, while improving the anti-inflammatory response of regulatory T cells, macrophages, and myeloid-derived suppressor cells in TIME, especially after irradiation. Finally, we presented an overview of dozens of promising therapeutics including pharmacological antagonists and specific antibodies targeting ADO receptors and ectonucleotidases CD39 or CD73 investigated in the clinic for cancer treatment, especially focusing on the preclinical studies and clinical trials being explored for blocking the purinergic signaling to enhance RT as a combination antitumor therapeutic strategy, which has a robust potential to be translated to the clinic in the future.

Dataset Information

The Achilles' heel of cancer: targeting tumors via lysosome-induced immunogenic cell death.

Publications

The Achilles' heel of cancer: targeting tumors via lysosome-induced immunogenic cell death.

Similar Datasets

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