Regulation of immune responses through CD39 and CD73 in cancer: Novel checkpoints

Baghbani, Elham; Noorolyai, Saeed; Shanehbandi, Dariush; Mokhtarzadeh, Ahad; Aghebati‐Maleki, Leili; Khaze, Vahid; Brunetti, Oronzo; Rahmani, Shima; Baghbanzadeh, Amir; Silvestris, Nicola; Baradaran, Behzad

doi:10.1016/j.lfs.2021.119826

Cited by 35 publications

(22 citation statements)

References 196 publications

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“…The immune system consists of innate and acquired immunity, which, once activated, clears infectious pathogens and tumor cells. Inhibitory pathways in antimicrobial or antitumor immune responses normally maintain auto-tolerance to avoid excessive damage and limit associated tissue damage ( 21 , 22 ). This receptor and ligand inhibitory pathways are known as “Immune Checkpoint” and are used by tumor cells to avoid Immune attack.…”

Section: Immune Checkpointmentioning

confidence: 99%

“…Each member of the adenosine signaling pathway constitutes a different drug target, meaning that it is possible for combined therapy with more than one drug to target this or complementary signaling pathway ( 33 ). Many of these combinations are currently in preclinical and clinical trials, such as anti-CD73 and anti-A2aR combinations, anti-CD73 and anti-PD-1 combinations, and anti-A2aR and anti-TIGIT antibody combinations ( 21 , 31 , 34 – 36 ) ( Table 1 ).…”

Section: Immune Checkpointmentioning

confidence: 99%

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Adenosinergic axis and immune checkpoint combination therapy in tumor: A new perspective for immunotherapy strategy

Liu

Shen

et al. 2022

Front. Immunol.

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There are two figures and one table in this review, the review consists of 5823 words, without the description of figures and table, but including references.Tumor cells escape anti-tumor immune responses in various ways, including functionally shaping the microenvironment through the secretion of various chemokines and, cytokines. Adenosine is a powerful immunosuppressive metabolite, that is frequently elevated in the extracellular tumor microenvironment (TME). Thus, it has recently been proposed as a novel antitumor immunoassay for targeting adenosine- generating enzymes, such as CD39, CD73, and adenosine receptors. In recent years, the discovery of the immune checkpoints, such as programmed cell death 1(PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4), has also greatly changed treatment methods and ideas for malignant tumors. Malignant tumor immunotherapy has been developed from point-to-point therapy targeting immune checkpoints, combining different points of different pathways to create a therapy based on the macroscopic immune regulatory system network. This article reviews the theoretical basis of the adenosine energy axis and immune checkpoint combined therapy for malignant tumors and the latest advances in malignant tumors.

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Section: Immune Checkpointmentioning

confidence: 99%

Section: Immune Checkpointmentioning

confidence: 99%

Adenosinergic axis and immune checkpoint combination therapy in tumor: A new perspective for immunotherapy strategy

Liu

Shen

et al. 2022

Front. Immunol.

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“…In addition, ATP and adenosine diphosphate (ADP) are cleaved into AMP by CD39, and then CD73 converts AMP to adenosine, thereby inhibiting the stimulation of CD8 + T cells, activating regulatory T cells (Tregs) and promoting the differentiation of M2 macrophages to inhibit antitumor immune responses ( 61 ). CD39 and CD73 together play an important role in transforming an ATP-mediated proinflammatory TME into an adenosine-mediated immunosuppressive microenvironment ( 62 ). Furthermore, ATP and its metabolites ADP and AMP all have immunosuppressive roles in inhibiting the abscopal effect; thus, sedatives of several target adenosines are being studied in the clinical practice to restore the abscopal effect.…”

Section: Roles Of Tumor-associated Molecular Patternsmentioning

confidence: 99%

Mechanism of exosomes in the tumor microenvironment in the abscopal effect (Review)

et al. 2022

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Previously, the abscopal effect, which is an antitumor therapeutic effect on untreated tumor locations elsewhere in the body as a result of treatment of the targeted region, was rarely reported, and its mechanism remains unknown. Increasing evidence has shown that the immune system is implicated in the abscopal effect, and that combining immunotherapy and radiation can assist to improve its frequency. Understanding how different types of cells and cell-derived exosomes cause the abscopal effect in the tumor microenvironment (TME) is crucial to increasing the clinical occurrence of the abscopal effect in the TME. Contents 1. Introduction 2. Immune mechanism of the abscopal effect 3. Role of tumor cells 4. Roles of tumor-associated molecular patterns 5. Clinical application 6. Conclusions

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“…Adenosine in particular generally acts as a brake on immune activity. The balance between ATP, AMP, and adenosine in the extracellular space is important for the regulation of tumor development and immune-escape mechanisms [124]. Adenosine can interact with numerous receptors from the adenosine receptor (AR) family (A1R, A2AR, A2BR, and A3R), which are present at the surface of various immune cells (DCs, macrophages, NK cells, T-or B-cells, and regulatory T-cells) [78,119,120,125,126].…”

Section: Exosomes and Cd73/cd39mentioning

confidence: 99%

Tumor-Derived Exosomes: Hidden Players in PD-1/PD-L1 Resistance

Vautrot

Bentayeb

Causse

et al. 2021

Cancers

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Recently, immunotherapy has garnered increasing importance in cancer therapy, leading to substantial improvements in patient care and survival. By blocking the immune checkpoints—protein regulators of the immune system—immunotherapy prevents immune tolerance toward tumors and reactivates the immune system, prompting it to fight cancer cell growth and diffusion. A widespread strategy for this is the blockade of the interaction between PD-L1 and PD-1. However, while patients generally respond well to immunotherapy, a certain proportion of patients present tumors that resist these treatments. This portion can be very high in some cancers and hinders cancer curability. For this reason, current efforts are focusing on combining PD-1/PD-L1 immunotherapy with the targeting of other immune checkpoints to counter resistance and achieve better results. Exosomes, small vesicles secreted by almost any cell, including tumor cells, have proven to be key actors in this resistance. The exosomes released by tumor cells spread the immune-suppressive properties of the tumor throughout the tumor microenvironment and participate in establishing metastatic niches. In this review, we will describe immune checkpoints and immune modulators whose presence in tumor-derived exosomes (TEXs) has been established. We will focus on the most promising proteins under scrutiny for use in combination with PD-1 blockade therapy in a clinical setting, such as PD-L1, CTLA-4, TIM-3, CD73/39, LAG-3, and TIGIT. We will explore the immunosuppressive impact of these exosomal proteins on a variety of immune cells. Finally, we will discuss how they can change the game in immunotherapy and guide therapeutic decisions, as well as the current limits of this approach. Depending on the viewpoint, these exosomal proteins may either provide key missing information on tumor growth and resistance mechanisms or they may be the next big challenge to overcome in improving cancer treatment.

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Regulation of immune responses through CD39 and CD73 in cancer: Novel checkpoints

Cited by 35 publications

References 196 publications

Adenosinergic axis and immune checkpoint combination therapy in tumor: A new perspective for immunotherapy strategy

Adenosinergic axis and immune checkpoint combination therapy in tumor: A new perspective for immunotherapy strategy

Mechanism of exosomes in the tumor microenvironment in the abscopal effect (Review)

Tumor-Derived Exosomes: Hidden Players in PD-1/PD-L1 Resistance

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