Natural Killer (NK) cell-mediated Antibody Dependent Cellular Cytotoxicity (ADCC), which is based on the recognition of IgG-opsonized target cells by the low affinity receptor for IgG FcgammaRIIIA/CD16, contributes to the elimination of tumor cells targeted by therapeutic monoclonal antibodies (mAbs). CD16 ligation also results in the production of interferon (IFN)-gamma which acts in the shaping of adaptive immune responses. Recently in order to amplify NK-mediated anti-tumor functions, combination strategies taking advantage of immune checkpoint-targeting mAbs have been proposed.
Memory NK cells are a recently identified long-lived and highly functional NK cell subset, featured by an enhanced capability to mediate CD16-dependent responses. In this context, we recently demonstrated their selective expansion in response to tumor cells targeted with anti-CD20 therapeutic mAbs.
In this project I want to deeply characterize tumor recognition receptor and immune checkpoint repertoire of anti-CD20-expanded memory NK cells and their functional relevance for direct and therapeutic mAb-mediated anti-tumor activity.
The expected results of this project allow to better define the phenotypic and functional heterogeneity of memory NK cells in terms of tumor recognition capability and their responsiveness to immune checkpoint-targeting mAbs, and will inspire the development of combined strategies aimed at potentiating their anti-tumor properties.
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