NKG2A Immune Checkpoint in Vδ2 T Cells: Emerging Application in Cancer Immunotherapy.

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Cazzetta, Valentina  ORCID logo  https://orcid.org/0000-0001-7183-2793
Depierreux, Delphine 
Mikulak, Joanna 

Immune regulation has revolutionized cancer treatment with the introduction of T-cell-targeted immune checkpoint inhibitors (ICIs). This successful immunotherapy has led to a more complete view of cancer that now considers not only the cancer cells to be targeted and destroyed but also the immune environment of the cancer cells. Current challenges associated with the enhancement of ICI effects are increasing the fraction of responding patients through personalized combinations of multiple ICIs and overcoming acquired resistance. This requires a complete overview of the anti-tumor immune response, which depends on a complex interplay between innate and adaptive immune cells with the tumor microenvironment. The NKG2A was revealed to be a key immune checkpoint for both Natural Killer (NK) cells and T cells. Monalizumab, a humanized anti-NKG2A antibody, enhances NK cell activity against various tumor cells and rescues CD8 αβ T cell function in combination with PD-1/PD-L1 blockade. In this review, we discuss the potential for targeting NKG2A expressed on tumor-sensing human γδ T cells, mostly on the specific Vδ2 T cell subset, in order to emphasize its importance and potential in the development of new ICI-based therapeutic approaches.


Peer reviewed: True

Funder: University of Milan

NKG2A, cancer immunotherapy, immune checkpoint inhibitors, inhibitory receptors, therapeutic monoclonal antibodies, γδ T cells
Journal Title
Cancers (Basel)
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Italian Ministry of Health (PE-2016-02363915)
Associazione Italiana per la Ricerca sul Cancro (IG 14687)
Intramural research and clinical funding programs of Humanitas Research Hospital (5 X 1000)
Wellbeing of Women (RG2331)
Wellcome Investigator Award (200841/Z/16/Z)