IMR Press / FBL / Volume 25 / Issue 1 / DOI: 10.2741/4795

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Metabolic approaches to rescue antitumor Vγ9Vδ2 T-cell functions in myeloma
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1 Laboratorio di Immunologia dei Tumori del Sangue (LITS), Centro Interdipartimentale di Ricerca in Biologia Molecolare (CIRBM), Università degli Studi di Torino, Turin, Italy;
2 Dipartimento di Oncologia, Università degli Studi di Torino, Turin, Italy;
3 SC Ematologia, AO S. Croce e Carle, Cuneo, Italy
Send correspondence to: Massimo Massaia, SC Ematologia, AO S. Croce e Carle, Via Michele Coppino 26, 12100 Cuneo, Italy; Tel.: 0171-642721, Fax: 0171-642209, E-mail:
Front. Biosci. (Landmark Ed) 2020, 25(1), 69–105;
Published: 1 January 2020
(This article belongs to the Special Issue Targeting of immune system in anti-tumor combined therapies)

Vγ9Vδ2 T cells are immune effector cells very well-suited for immunotherapy, but clinical results have been disappointing in multiple myeloma (MM) and other cancers. We have shown that Vγ9Vδ2 T cells are victimized prematurely by the immune suppressive tumor microenvironment (TME) established by myeloma and neighbouring cells in the bone marrow (BM) of MM patients. One major mechanism is the highly redundant expression of multiple immunecheckpoints/immune checkpoint-ligands (ICP/ICP-L) in the TME impairing antimyeloma Vγ9Vδ2 T-cell immune responses. Another major immune suppressive mechanism is the metabolic reset driven by myeloma cells in the TME to satisfy their energetic needs to the detriment of effector cells. Recently, it has become clear that the ICP/ICP-L circuitry and metabolic checkpoints (MCP) jointly operate in the TME of cancer patients to promote tumor cell growth and suppress antitumor immune responses. In this review, we discuss the possible interactions between ICP/ICP-L and MCP in the TME of MM patients that may compromise the immune competence of BM Vγ9Vδ2 T cells, envisaging novel combination therapies to improve the outcome of immune-based interventions.

Metabolic Checkpoints
Vγ9Vδ2 T cells
Immune Checkpoint
Multiple Myeloma
Tumor Microenvironment
Figure 1
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