Targeting CD73 to augment cancer immunotherapy

Roh, Meejeon; Wainwright, Derek A.; Wu, Jennifer D.; Wan, Yong; Zhang, Bin

doi:10.1016/j.coph.2020.07.001

Cited by 97 publications

(87 citation statements)

References 124 publications

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“…This nanoplatform induced a high rate of apoptosis and slowed down tumor cell growth [ 164 ]. Another option to increase eATP in a controlled fashion may be CD39 and/or CD73 targeting [ 165 , 166 ] ( Table 1 ). Recent studies demonstrated that the use of anti-CD39 antibodies boosts the eATP-P2X7-inflammasome-IL-18 axis, thus resulting in a decrease of macrophage recruitment and an increase in effector CD8 + T cells in the TME [ 167 ].…”

Section: Extracellular Atp As a Target For Cancer Therapymentioning

confidence: 99%

Extracellular ATP: A Feasible Target for Cancer Therapy

Vultaggio-Poma

Sarti

Virgilio

2020

Cells

166

216

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Adenosine triphosphate (ATP) is one of the main biochemical components of the tumor microenvironment (TME), where it can promote tumor progression or tumor suppression depending on its concentration and on the specific ecto-nucleotidases and receptors expressed by immune and cancer cells. ATP can be released from cells via both specific and nonspecific pathways. A non-regulated release occurs from dying and damaged cells, whereas active release involves exocytotic granules, plasma membrane-derived microvesicles, specific ATP-binding cassette (ABC) transporters and membrane channels (connexin hemichannels, pannexin 1 (PANX1), calcium homeostasis modulator 1 (CALHM1), volume-regulated anion channels (VRACs) and maxi-anion channels (MACs)). Extracellular ATP acts at P2 purinergic receptors, among which P2X7R is a key mediator of the final ATP-dependent biological effects. Over the years, P2 receptor- or ecto-nucleotidase-targeting for cancer therapy has been proposed and actively investigated, while comparatively fewer studies have explored the suitability of TME ATP as a target. In this review, we briefly summarize the available evidence suggesting that TME ATP has a central role in determining tumor fate and is, therefore, a suitable target for cancer therapy.

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Section: Extracellular Atp As a Target For Cancer Therapymentioning

confidence: 99%

Extracellular ATP: A Feasible Target for Cancer Therapy

Vultaggio-Poma

Sarti

Virgilio

2020

Cells

166

216

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“…Perturbation of these pathways reduces MDSC recruitment to the tumor site ( 8 , 107 , 108 ), increases CD8 T cells in the TME ( 8 , 107 , 108 ), and converts the tumor to immunotherapy-sensitive ( 8 ). MDSC reduction can be achieved via depletion, using CD33-specific immunotoxin Gemtuzumab ozogamicin ( 110 ) or ADH-503, a small-molecule agonist for CD11b ( 111 ), while the immunosuppressive activity of MDSCs can be blunted using anti-TIGIT ( 112 ) or CD73 blockade ( 113 ).…”

Section: Simulating a “Small” Immune Microenvironmentmentioning

confidence: 99%

Tumor Burden and Immunotherapy: Impact on Immune Infiltration and Therapeutic Outcomes

2021

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Cancer immunotherapy has revolutionized the treatment landscape in medical oncology, but its efficacy has been variable across patients. Biomarkers to predict such differential response to immunotherapy include cytotoxic T lymphocyte infiltration, tumor mutational burden, and microsatellite instability. A growing number of studies also suggest that baseline tumor burden, or tumor size, predicts response to immunotherapy. In this review, we discuss the changes in immune profile and therapeutic responses that occur with increasing tumor size. We also overview therapeutic approaches to reduce tumor burden and favorably modulate the immune microenvironment of larger tumors.

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“…CD73 is a metabolic immune checkpoint responsible for coordinating the level of extracellular adenosine, which can control the inflammatory response in the microenvironment of tissues that are stressed or damaged ( 47 ). In a variety of tumors, dysregulations of CD73 expression and activity have been reported ( 48 – 50 ). A recent study points out that tumor-infiltrating NK cells up-regulate the expression of CD73, and these CD73 + NK cells will undergo transcriptional reprogramming, and increase the production of IL-10 by up-regulating the transcription activity of STAT3, thereby inhibiting the activity of CD4 + T cells ( 15 ) ( Figure 1 ).…”

Section: Molecular Mechanisms Controlling Il-10 Expression In Ilcsmentioning

confidence: 99%

IL-10-Producing ILCs: Molecular Mechanisms and Disease Relevance

Sun

Wu²,

Zhang³

et al. 2021

Front. Immunol.

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Innate lymphoid cells (ILCs) are mainly composed of natural killer (NK) cells and helper-like lymphoid cells, which play a vital role in maintaining tissue homeostasis, enhancing adaptive immunity and regulating tissue inflammation. Alteration of the distribution and function of ILCs subgroups are closely related to the pathogenesis of inflammatory diseases and cancers. Interleukin-10 (IL-10) is a highly pleiotropic cytokine, and can be secreted by several cell types, among of which ILCs are recently verified to be a key source of IL-10. So far, the stable production of IL-10 can only be observed in certain NK subsets and ILC2s. Though the regulatory mechanisms for ILCs to produce IL-10 are pivotal for understanding ILCs and potential intervenes of diseases, which however is largely unknown yet. The published studies show that ILCs do not share exactly the same mechanisms for IL-10 production with helper T cells. In this review, the molecular mechanisms regulating IL-10 production in NK cells and ILC2s are discussed in details for the first time, and the role of IL-10-producing ILCs in diseases such as infections, allergies, and cancers are summarized.

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Targeting CD73 to augment cancer immunotherapy

Cited by 97 publications

References 124 publications

Extracellular ATP: A Feasible Target for Cancer Therapy

Extracellular ATP: A Feasible Target for Cancer Therapy

Tumor Burden and Immunotherapy: Impact on Immune Infiltration and Therapeutic Outcomes

IL-10-Producing ILCs: Molecular Mechanisms and Disease Relevance

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