CD39 – A bright target for cancer immunotherapy

Guo, Shuwei; Han, Fengfeng; Zhu, Weijun

doi:10.1016/j.biopha.2022.113066

Cited by 29 publications

(26 citation statements)

References 153 publications

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“…Among these, the ectonucleotidase, CD39, is increasing reported as a faithful marker of tumor antigen experienced CD8 + T cells 16,28 , particularly among terminally exhausted 3,5 . An increasing number of preclinical studies have revealed the therapeutic potential of CD39 inhibition-in addition to other targets in adenosine metabolism (spurring several phase I/II trials in solid tumors and lymphoma with antibody or inhibitor therapy 43 ). In solid tumors, the metabolic features of tumor cells 15 and the resulting hypoxic 13,14 and nutrient dearth microenvironment 6 accelerates CD8 + T cell dysfunction and diminishes efficacy of checkpoint blockade therapy.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia drives CD39-dependent suppressor function in exhausted T cells to limit antitumor immunity

et al. 2022

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Extended Data Fig. 6 | Cd4-driven Cre recombinase expression efficiently deletes CD39 on CD8 + TIL. (a, b) TIL analysis of CD39 and inhibitory expression in CD8 + T cells from Cd4 Cre Entpd1 f/f mice. (c) Cell counts per milligram of tumor mass from experiments in Extended Data Fig. 6a, b. (d) Tumor areas at day 14 from experiments in Fig. 2f. (e) Suppression assay of Cd4 Cre Entpd1 f/f Thy1.1 + CD44 + OT-I T eff cells isolated from day 8 of acute Vaccinia OVA infection. (f) CD39 expression on TIL tT ex cells or Vaccinia OVA OT-I T cells in suppression assay co-cultures. (g) Suppression assay of B16-F10-derived CD8 + tT ex cells co-cultured with OT-I TCR transgenic CD8 + T cells. Culture were stimulated with either anti-CD3 antibodies as before, or OT-I specific peptide, SIIFEKL. (h-j) Flow cytometric analysis of TIL following suppression assay from Extended Data Fig. 6g. Statistics are Mann-Whitney (B-D,H-J) and linear regression (E,G) with * p < 0.05, * * p < 0.01,

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Section: Discussionmentioning

confidence: 99%

Hypoxia drives CD39-dependent suppressor function in exhausted T cells to limit antitumor immunity

et al. 2022

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“…Adenosine is an important regulator of metabolism and a key immune checkpoint regulator associated with tumors evading the host immune system ( 1 – 4 ). Extracellular adenosine (eADO) inhibits immune function.…”

Section: Adenosinergic Axis and Tumor Immunologymentioning

confidence: 99%

“…CD39 is highly expressed in the tumor endothelium of the TME and on most immunocytes (including macrophages, myeloid cells, and FOXP3+ regulatory T cells (Treg) ( 3 ). The CD39 topological domain consists of two transmembrane domains, including short cytoplasmic N-and C-terminal segments and a large extracellular hydrophobic domain containing the active site ( 15 ).The extracellular domain contains five conserved propyrylase regions from ACR1 to ACR5, among which the amino acid sequences of ACR1 and ACR5 contain phosphate-binding motifs, which are believed to be critical for stabilizing the interaction between the enzyme and its nucleotide substrate during phosphate cleavage ( 4 ). CD39 can stabilize FOXP3+Tregs, contribute to their immunosuppressive function ( 16 ), promote type I Treg differentiation, produce IL-10, and restrict the activation of NLRP3 inflammatory bodies in dendritic cells (DCs) ( 2 , 13 , 14 ).…”

Section: Adenosinergic Axis and Tumor Immunologymentioning

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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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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“…These molecules are linked to CD8+T cell exhaustion ( Gabriely et al, 2017 ; Philip and Schietinger, 2022 ). CD39 on the surface of CD8+ TRM cells also promotes tumor growth ( Guo et al, 2022 ).…”

Section: Effector Phasementioning

confidence: 99%

The soldiers needed to be awakened: Tumor-infiltrating immune cells

Wang

Zhuling³

et al. 2022

Front. Genet.

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In the tumor microenvironment, tumor-infiltrating immune cells (TIICs) are a key component. Different types of TIICs play distinct roles. CD8+ T cells and natural killer (NK) cells could secrete soluble factors to hinder tumor cell growth, whereas regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) release inhibitory factors to promote tumor growth and progression. In the meantime, a growing body of evidence illustrates that the balance between pro- and anti-tumor responses of TIICs is associated with the prognosis in the tumor microenvironment. Therefore, in order to boost anti-tumor response and improve the clinical outcome of tumor patients, a variety of anti-tumor strategies for targeting TIICs based on their respective functions have been developed and obtained good treatment benefits, including mainly immune checkpoint blockade (ICB), adoptive cell therapies (ACT), chimeric antigen receptor (CAR) T cells, and various monoclonal antibodies. In recent years, the tumor-specific features of immune cells are further investigated by various methods, such as using single-cell RNA sequencing (scRNA-seq), and the results indicate that these cells have diverse phenotypes in different types of tumors and emerge inconsistent therapeutic responses. Hence, we concluded the recent advances in tumor-infiltrating immune cells, including functions, prognostic values, and various immunotherapy strategies for each immune cell in different tumors.

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CD39 – A bright target for cancer immunotherapy

Cited by 29 publications

References 153 publications

Hypoxia drives CD39-dependent suppressor function in exhausted T cells to limit antitumor immunity

Hypoxia drives CD39-dependent suppressor function in exhausted T cells to limit antitumor immunity

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

The soldiers needed to be awakened: Tumor-infiltrating immune cells

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