Genetically driven <scp>CD39</scp> expression shapes human tumor‐infiltrating <scp>CD8</scp><sup>+</sup> T‐cell functions

Gallerano, Daniela; Ciminati, Selina; Grimaldi, Alfonso; Piconese, Silvia; Cammarata, Ilenia; Focaccetti, Chiara; Pacella, Ilenia; Accapezzato, Daniele; Lancellotti, Francesco; Sacco, L.; Caronna, Roberto; Melaiu, Ombretta; Fruci, Doriana; D’Oria, Valentina; Manzi, Emy; Sagnotta, Andrea; Parrino, Chiara; Coletta, Diego; Peruzzi, Giovanna; Terenzi, Valentina; Battisti, Andrea; Cassoni, Andrea; Fadda, Maria Teresa; Brozzetti, Stefania; Fazzi, Katia; Grazi, Gian Luca; Valentini, Valentino; Chirletti, Piero; Polimeni, Antonella; Barnaba, Vincenzo; Timperi, Eleonora

doi:10.1002/ijc.33131

Cited by 35 publications

(33 citation statements)

References 47 publications

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“…Most data described a strong correlation between elevated CD73 levels and unfavorable clinical outcomes, as was observed for CD39 [ 36 , 37 , 38 , 39 ]. Through CD39 and CD73 blockade, likely limiting the conversion of ATP/AMP into adenosine, many mouse, human and in vitro studies showed inhibition of both tumor growth and metastasis formation, generally associated with an increase of NK and/or CD8 T cell immune-mediated antitumor responses [ 21 , 25 , 33 , 40 , 41 , 42 , 43 , 44 ].…”

Section: Adenosine Pathway and Cd39/cd73 Expression In The Tumor Microenvironmentmentioning

confidence: 99%

CD39 Regulation and Functions in T Cells

Timperi

Barnaba

2021

IJMS

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CD39 is an enzyme which is responsible, together with CD73, for a cascade converting adenosine triphosphate into adenosine diphosphate and cyclic adenosine monophosphate, ultimately leading to the release of an immunosuppressive form of adenosine in the tumor microenvironment. Here, we first review the environmental and genetic factors shaping CD39 expression. Second, we report CD39 functions in the T cell compartment, highlighting its role in regulatory T cells, conventional CD4+ T cells and CD8+ T cells. Finally, we compile a list of studies, from preclinical models to clinical trials, which have made essential contributions to the discovery of novel combinatorial approaches in the treatment of cancer.

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Section: Adenosine Pathway and Cd39/cd73 Expression In The Tumor Microenvironmentmentioning

confidence: 99%

CD39 Regulation and Functions in T Cells

Timperi

Barnaba

2021

IJMS

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“…ATP hydrolysis drives the immune response to collaborate with tumor growth, making the CD39/CD73 axis an important regulator of immune effector function. This is a hallmark of cancer ( 78 – 81 ). Interestingly, CD39 inhibition can restore TIL function, and a single nucleotide polymorphism has been identified that may predict dysfunctional CD39 + expression in TILs in some solid tumors ( 81 ).…”

Section: Immune System In Gliomasmentioning

confidence: 99%

Immunosuppression in Gliomas via PD-1/PD-L1 Axis and Adenosine Pathway

et al. 2021

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Glioblastoma is the most malignant and lethal subtype of glioma. Despite progress in therapeutic approaches, issues with the tumor immune landscape persist. Multiple immunosuppression pathways coexist in the tumor microenvironment, which can determine tumor progression and therapy outcomes. Research in immune checkpoints, such as the PD-1/PD-L1 axis, has renewed the interest in immune-based cancer therapies due to their ability to prevent immunosuppression against tumors. However, PD-1/PD-L1 blockage is not completely effective, as some patients remain unresponsive to such treatment. The production of adenosine is a major obstacle for the efficacy of immune therapies and is a key source of innate or adaptive resistance. In general, adenosine promotes the pro-tumor immune response, dictates the profile of suppressive immune cells, modulates the release of anti-inflammatory cytokines, and induces the expression of alternative immune checkpoint molecules, such as PD-1, thus maintaining a loop of immunosuppression. In this context, this review aims to depict the complexity of the immunosuppression in glioma microenvironment. We primarily consider the PD-1/PD-L1 axis and adenosine pathway, which may be critical points of resistance and potential targets for tumor treatment strategies.

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“…Simoni et al found that CD39 may be a predictive biomarker for patients to respond to CD8 + TIL targeted cancer immunotherapy. Whether CD8+ TIL cells express CD39 or can predict the response degree of patients to PD-1 antibody therapy, it is of great help to screen more potential anticancer T cells in TIL and CAR-T cell therapy, and further expand the immunotherapy (80)(81)(82).…”

Section: Cd39mentioning

confidence: 99%

The Mechanism of Stimulating and Mobilizing the Immune System Enhancing the Anti-Tumor Immunity

Zhu

2021

Front. Immunol.

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Cancer immunotherapy is a kind of therapy that can control and eliminate tumors by restarting and maintaining the tumor-immune cycle and restoring the body’s normal anti-tumor immune response. Although immunotherapy has great potential, it is currently only applicable to patients with certain types of tumors, such as melanoma, lung cancer, and cancer with high mutation load and microsatellite instability, and even in these types of tumors, immunotherapy is not effective for all patients. In order to enhance the effectiveness of tumor immunotherapy, this article reviews the research progress of tumor microenvironment immunotherapy, and studies the mechanism of stimulating and mobilizing immune system to enhance anti-tumor immunity. In this review, we focused on immunotherapy against tumor microenvironment (TME) and discussed the important research progress. TME is the environment for the survival and development of tumor cells, which is composed of cell components and non-cell components; immunotherapy for TME by stimulating or mobilizing the immune system of the body, enhancing the anti-tumor immunity. The checkpoint inhibitors can effectively block the inhibitory immunoregulation, indirectly strengthen the anti-tumor immune response and improve the effect of immunotherapy. We also found the checkpoint inhibitors have brought great changes to the treatment model of advanced tumors, but the clinical treatment results show great individual differences. Based on the close attention to the future development trend of immunotherapy, this study summarized the latest progress of immunotherapy and pointed out a new direction. To study the mechanism of stimulating and mobilizing the immune system to enhance anti-tumor immunity can provide new opportunities for cancer treatment, expand the clinical application scope and effective population of cancer immunotherapy, and improve the survival rate of cancer patients.

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Genetically driven CD39 expression shapes human tumor‐infiltrating CD8⁺ T‐cell functions

Cited by 35 publications

References 47 publications

CD39 Regulation and Functions in T Cells

CD39 Regulation and Functions in T Cells

Immunosuppression in Gliomas via PD-1/PD-L1 Axis and Adenosine Pathway

The Mechanism of Stimulating and Mobilizing the Immune System Enhancing the Anti-Tumor Immunity

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Genetically driven CD39 expression shapes human tumor‐infiltrating CD8+ T‐cell functions

Cited by 35 publications

References 47 publications

CD39 Regulation and Functions in T Cells

CD39 Regulation and Functions in T Cells

Immunosuppression in Gliomas via PD-1/PD-L1 Axis and Adenosine Pathway

The Mechanism of Stimulating and Mobilizing the Immune System Enhancing the Anti-Tumor Immunity

Contact Info

Product

Resources

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Genetically driven CD39 expression shapes human tumor‐infiltrating CD8⁺ T‐cell functions