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Radiotherapy induced immunogenic cell death by remodeling tumor immune microenvironment.

ABSTRACT: Emerging evidence indicates that the induction of radiotherapy(RT) on the immunogenic cell death (ICD) is not only dependent on its direct cytotoxic effect, changes in the tumor immune microenvironment also play an important role in it. Tumor immune microenvironment (TIME) refers to the immune microenvironment that tumor cells exist, including tumor cells, inflammatory cells, immune cells, various signaling molecules and extracellular matrix. TIME has a barrier effect on the anti-tumor function of immune cells, which can inhibit all stages of anti-tumor immune response. The remodeling of TIME caused by RT may affect the degree of immunogenicity, and make it change from immunosuppressive phenotype to immunostimulatory phenotype. It is of great significance to reveal the causes of immune escape of tumor cells, especially for the treatment of drug-resistant tumor. In this review, we focus on the effect of RT on the TIME, the mechanism of RT in reversing the TIME to suppress intrinsic immunity, and the sensitization effect of the remodeling of TIME caused by RT on the effectiveness of immunotherapy.

SUBMITTER: Zhu S

PROVIDER: S-EPMC9753984 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Radiotherapy induced immunogenic cell death by remodeling tumor immune microenvironment.

Zhu Songxin S Wang Yuming Y Tang Jun J Cao Min M

Frontiers in immunology 20221201

Emerging evidence indicates that the induction of radiotherapy(RT) on the immunogenic cell death (ICD) is not only dependent on its direct cytotoxic effect, changes in the tumor immune microenvironment also play an important role in it. Tumor immune microenvironment (TIME) refers to the immune microenvironment that tumor cells exist, including tumor cells, inflammatory cells, immune cells, various signaling molecules and extracellular matrix. TIME has a barrier effect on the anti-tumor function ...[more]

PMID: 36532071

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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

Radiotherapy induced immunogenic cell death by remodeling tumor immune microenvironment.

Publications

Radiotherapy induced immunogenic cell death by remodeling tumor immune microenvironment.

Similar Datasets

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