Blockade of CD73 delays glioblastoma growth by modulating the immune environment

Azambuja, Juliana H.; Schuh, Roselena Silvestri; Michels, Luana Roberta; Iser, Isabele Cristiana; Beckenkamp, Liziane Raquel; Roliano, Gabriela Gonçalves; Lenz, Gabriela Spies; Scholl, Juliete Nathali; Sévigny, Jean; Wink, Márcia Rosângela; Stefani, Marco Antônio; Battastini, Ana Maria Oliveira; Figueiró, Fabrício; Teixeira, Hélder Ferreira; Braganhol, Elizandra

doi:10.1007/s00262-020-02569-w

Cited by 39 publications

(29 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD73 contributes to tumor immune escape by converting immune-activating ATP into immunosuppressive adenosine. CD73hi macrophages potentially suppress infiltrating immune cells through adenosine production (82).…”

Section: Remodeling Myeloid Cell Environmentsmentioning

confidence: 99%

Strategies to Enhance the Efficacy of T-Cell Therapy for Central Nervous System Tumors

et al. 2020

View full text Add to dashboard Cite

Section: Remodeling Myeloid Cell Environmentsmentioning

confidence: 99%

Strategies to Enhance the Efficacy of T-Cell Therapy for Central Nervous System Tumors

et al. 2020

View full text Add to dashboard Cite

“…Treg-mediated immunosuppression has been targeted to enhance the efficacy of natural or induced antitumoral immunity mainly in preclinical models of GBM. This includes depletion of Treg by anti-CD25 antibodies ( 145 , 222 , 226 , 227 ), interference with their immunosuppressive activity, e.g., by blocking surface molecules such as CTLA-4 ( 222 , 228 , 229 ), TIGIT ( 230 ), Tim-3 ( 231 ), and PD-1 ( 229 , 230 , 232 ) or enzymes like ecto-5′-nucleotidase (CD73) ( 233 ) and IDO ( 229 ), or by preventing the accumulation of Treg in the TME by blocking CCR4-mediated migration ( 225 ). Irrespective of the approach, these studies could document a beneficial effect, with increased survival and reduction of tumor burden associated with restoration of antitumoral immunity, particularly when different strategies were combined.…”

Section: Immunosuppression and Immune Checkpoint Regulationmentioning

confidence: 99%

Dendritic Cell Vaccination of Glioblastoma: Road to Success or Dead End

Datsi

Sorg

2021

Front. Immunol.

View full text Add to dashboard Cite

Glioblastomas (GBM) are the most frequent and aggressive malignant primary brain tumor and remains a therapeutic challenge: even after multimodal therapy, median survival of patients is only 15 months. Dendritic cell vaccination (DCV) is an active immunotherapy that aims at inducing an antitumoral immune response. Numerous DCV trials have been performed, vaccinating hundreds of GBM patients and confirming feasibility and safety. Many of these studies reported induction of an antitumoral immune response and indicated improved survival after DCV. However, two controlled randomized trials failed to detect a survival benefit. This raises the question of whether the promising concept of DCV may not hold true or whether we are not yet realizing the full potential of this therapeutic approach. Here, we discuss the results of recent vaccination trials, relevant parameters of the vaccines themselves and of their application, and possible synergies between DCV and other therapeutic approaches targeting the immunosuppressive microenvironment of GBM.

show abstract

“…51 Along these lines, inhibition of CD73 with a small interfering RNA (siRNA) emulsion given intranasally was associated with reduced glioblastoma growth and proportionally fewer CD206 + macrophages in a preclinical model. 52 Although the adenosine pathway Review has a broad immunosuppressive effect in the tumor microenvironment, 53 specific and possibly inducible ablation of CD73, CD39, and adenosine receptor expression in macrophages will be essential to delineate the impact of adenosine on TAM function.…”

Section: Adenosine Receptorsmentioning

confidence: 99%

Turning enemies into allies—reprogramming tumor-associated macrophages for cancer therapy

Molgora

Colonna

2021

Med

View full text Add to dashboard Cite

Checkpoint blockade therapies that target inhibitory receptors on T cells have revolutionized clinical oncology. Antibodies targeting CTLA-4 or the PD-1/PD-1 ligand (PD-L1) axis are now successfully used alone or in combination with chemotherapy for numerous tumor types. Despite the clinical success of checkpoint blockade therapies, tumors exploit multiple mechanisms to escape or subvert the anti-tumor T cell response. Within the tumor microenvironment, tumor-associated macrophages (TAMs) can suppress T cell responses and facilitate tumor growth in various ways, ultimately debilitating clinical responses to T cell checkpoint inhibitors. There is therefore significant interest in identifying biologicals and drugs that target immunosuppressive TAM within the tumor microenvironment and can be combined with immune checkpoint inhibitors. Here, we review approaches that are currently being evaluated to convert immunosuppressive TAM into immunostimulatory macrophages that promote T cell responses and tumor elimination.

show abstract

Blockade of CD73 delays glioblastoma growth by modulating the immune environment

Cited by 39 publications

References 41 publications

Strategies to Enhance the Efficacy of T-Cell Therapy for Central Nervous System Tumors

Strategies to Enhance the Efficacy of T-Cell Therapy for Central Nervous System Tumors

Dendritic Cell Vaccination of Glioblastoma: Road to Success or Dead End

Turning enemies into allies—reprogramming tumor-associated macrophages for cancer therapy

Contact Info

Product

Resources

About