Vγ9Vδ2 T Cells as Strategic Weapons to Improve the Potency of Immune Checkpoint Blockade and Immune Interventions in Human Myeloma

Frontiers in Oncology

Chiara Riganti¹  Assunta Melaccio²  Barbara Castella³  Myriam Foglietta⁴  Massimo Massaia⁴ 

[1] Dipartimento di Oncologia, Università degli Studi di Torino, Turin, Italy;Dipartimento di Scienze Biomediche ed Oncologia Umana, Sezione di Medicina Interna ed Oncologia, Università degli studi di Bari “A. Moro”, Bari, Italy;Laboratorio di Immunologia dei Tumori del Sangue, Centro Interdipartimentale di Ricerca in Biologia Molecolare, Università degli Studi di Torino, Turin, Italy;SC Ematologia, AO S.Croce e Carle, Cuneo, Italy;

关键词: Vγ9Vδ2 T cells;    immune checkpoint blockade;    immunotherapy;    tumor vaccination;    multiple myeloma;   

DOI  :  10.3389/fonc.2018.00508

来源: DOAJ

【 摘 要 】

The advent of immune checkpoint (ICP) blockade has introduced an unprecedented paradigm shift in the treatment of cancer. Though very promising, there is still a substantial proportion of patients who do not respond or develop resistance to ICP blockade. In vitro and in vivo models are eagerly needed to identify mechanisms to maximize the immune potency of ICP blockade and overcome primary and acquired resistance to ICP blockade. Vγ9Vδ2 T cells isolated from the bone marrow (BM) from multiple myeloma (MM) are excellent tools to investigate the mechanisms of resistance to PD-1 blockade and to decipher the network of mutual interactions between PD-1 and the immune suppressive tumor microenvironment (TME). Vγ9Vδ2 T cells can easily be interrogated to dissect the progressive immune competence impairment generated in the TME by the long-lasting exposure to myeloma cellss. BM MM Vγ9Vδ2 T cells are PD-1+ and anergic to phosphoantigen (pAg) stimulation; notably, single agent PD-1 blockade is insufficient to fully recover their anti-tumor activity in vitro indicating that additional players are involved in the anergy of Vγ9Vδ2 T cells. In this mini-review we will discuss the value of Vγ9Vδ2 T cells as investigational tools to improve the potency of ICP blockade and immune interventions in MM.

【 授权许可】

Unknown