Metabolic approaches to rescue antitumor V gamma 9V delta 2 T-cell functions in myeloma

Massaia, Massimo

doi:10.2741/4795

Cited by 5 publications

(3 citation statements)

References 80 publications

(96 reference statements)

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“…Combining ICP/ICP-L inhibitors with lower therapeutic concentrations of glycolytic inhibitors, to mitigate side effects, can synergistically enhance the antitumor activity of γδ TILs. ICP/ICP-L inhibitors can also be used in conjunction with AKT/mTOR inhibitors to facilitate a more balanced redistribution of glucose in the TME [ 80 ].…”

Section: Combination Therapy Targeting Icps To Enhance γδ T Cells Ant...mentioning

confidence: 99%

“…The exhaustion phenotype of PD-L1 high γδ T cells in tumors is mediated by the hypoxic environment, suggesting that combination therapy targeting HIF1-α and blocking PD-1/PD-L1 signaling may effectively reverse hypoxia-induced immunosuppression [ 59 ]. Additionally, arginine deprivation has been found to inhibit the Vγ9Vδ2 T cell-mediated antitumor immune response thus the inhibition of arginase 1 (Arg1) can restore the capability of γδ T cells to secrete IFN-γ and effectively eliminate MDSC-induced immunosuppressive Daudi and Jurkat cells [ 80 ]. An IDO inhibitor (1-MT) can also rescue dysfunctional or exhausted T cells by increasing tryptophan levels and enhancing the cytotoxicity of Vγ9Vδ2 T cells by increasing the generation of PRF1 in TNBC [ 37 ].…”

Section: Combination Therapy Targeting Icps To Enhance γδ T Cells Ant...mentioning

confidence: 99%

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γδ T cells and the PD-1/PD-L1 axis: a love–hate relationship in the tumor microenvironment

Liu,

Wu,

Yang

et al. 2024

J Transl Med

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Gamma delta (γδ) T cells demonstrate strong cytotoxicity against diverse cancer cell types in an MHC-independent manner, rendering them promising contenders for cancer therapy. Although amplification and adoptive transfer of γδ T cells are being evaluated in the clinic, their therapeutic efficacy remains unsatisfactory, primarily due to the influence of the immunosuppressive tumor microenvironment (TME). Currently, the utilization of targeted therapeutic antibodies against inhibitory immune checkpoint (ICP) molecules is a viable approach to counteract the immunosuppressive consequences of the TME. Notably, PD-1/PD-L1 checkpoint inhibitors are considered primary treatment options for diverse malignancies, with the objective of preserving the response of αβ T cells. However, γδ T cells also infiltrate various human cancers and are important participants in cancer immunity, thereby influencing patient prognosis. Hence, it is imperative to comprehend the reciprocal impact of the PD-1/PD-L1 axis on γδ T cells. This understanding can serve as a therapeutic foundation for improving γδ T cells adoptive transfer therapy and may offer a novel avenue for future combined immunotherapeutic approaches.

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Section: Combination Therapy Targeting Icps To Enhance γδ T Cells Ant...mentioning

confidence: 99%

Section: Combination Therapy Targeting Icps To Enhance γδ T Cells Ant...mentioning

confidence: 99%

γδ T cells and the PD-1/PD-L1 axis: a love–hate relationship in the tumor microenvironment

Liu,

Wu,

Yang

et al. 2024

J Transl Med

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“…Arginase I inhibition is another metabolic approach that can indirectly promote the antitumor activity of Vγ9Vδ2 T cells by restraining the suppressor activity of MDSC ( 73 , 153 ). We have recently reviewed the role of metabolic checkpoints compromising the immune competence of Vγ9Vδ2 T cells in MM, and the possible interventions to recover their antitumor activity ( 154 ).…”

Section: Strategies To Bring Vγ9vδ2 T-cell Immune Interventions To Pr...mentioning

confidence: 99%

Vγ9Vδ2 T-cell immunotherapy in blood cancers: ready for prime time?

2023

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In the last years, the tumor microenvironment (TME) has emerged as a promising target for therapeutic interventions in cancer. Cancer cells are highly dependent on the TME to growth and evade the immune system. Three major cell subpopulations are facing each other in the TME: cancer cells, immune suppressor cells, and immune effector cells. These interactions are influenced by the tumor stroma which is composed of extracellular matrix, bystander cells, cytokines, and soluble factors. The TME can be very different depending on the tissue where cancer arises as in solid tumors vs blood cancers. Several studies have shown correlations between the clinical outcome and specific patterns of TME immune cell infiltration. In the recent years, a growing body of evidence suggests that unconventional T cells like natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) cells, and γδ T cells are key players in the protumor or antitumor TME commitment in solid tumors and blood cancers. In this review, we will focus on γδ T cells, especially Vγ9Vδ2 T cells, to discuss their peculiarities, pros, and cons as potential targets of therapeutic interventions in blood cancers.

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Gamma delta T-cell-based immune checkpoint therapy: attractive candidate for antitumor treatment

et al. 2023

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As a nontraditional T-cell subgroup, γδT cells have gained popularity in the field of immunotherapy in recent years. They have extraordinary antitumor potential and prospects for clinical application. Immune checkpoint inhibitors (ICIs), which are efficacious in tumor patients, have become pioneer drugs in the field of tumor immunotherapy since they were incorporated into clinical practice. In addition, γδT cells that have infiltrated into tumor tissues are found to be in a state of exhaustion or anergy, and there is upregulation of many immune checkpoints (ICs) on their surface, suggesting that γδT cells have a similar ability to respond to ICIs as traditional effector T cells. Studies have shown that targeting ICs can reverse the dysfunctional state of γδT cells in the tumor microenvironment (TME) and exert antitumor effects by improving γδT-cell proliferation and activation and enhancing cytotoxicity. Clarification of the functional state of γδT cells in the TME and the mechanisms underlying their interaction with ICs will solidify ICIs combined with γδT cells as a good treatment option.

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Metabolic approaches to rescue antitumor V gamma 9V delta 2 T-cell functions in myeloma

Cited by 5 publications

References 80 publications

γδ T cells and the PD-1/PD-L1 axis: a love–hate relationship in the tumor microenvironment

γδ T cells and the PD-1/PD-L1 axis: a love–hate relationship in the tumor microenvironment

Vγ9Vδ2 T-cell immunotherapy in blood cancers: ready for prime time?

Gamma delta T-cell-based immune checkpoint therapy: attractive candidate for antitumor treatment

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