Designing Cancer Immunotherapies That Engage T Cells and NK Cells

T cells and natural killer (NK) cells have complementary roles in tumor immunity, and dual T cell and NK cell attack thus offers opportunities to deepen the impact of immunotherapy. Recent work has also shown that NK cells play an important role in recruiting dendritic cells to tumors and thus enhan...

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Bibliographic Details
Published in:Annual review of immunology 2023-04, Vol.41 (1), p.17-38
Main Authors: Kyrysyuk, Oleksandr, Wucherpfennig, Kai W
Format: Article
Language:English
Subjects:
Animals
cancer immunotherapy
CD8-Positive T-Lymphocytes
Histocompatibility Antigens Class I
Humans
Immunity, Cellular
Immunotherapy
Killer Cells, Natural
natural killer cells
Neoplasms
T cells
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Summary:T cells and natural killer (NK) cells have complementary roles in tumor immunity, and dual T cell and NK cell attack thus offers opportunities to deepen the impact of immunotherapy. Recent work has also shown that NK cells play an important role in recruiting dendritic cells to tumors and thus enhance induction of CD8 T cell responses, while IL-2 secreted by T cells activates NK cells. Targeting of immune evasion mechanisms from the activating NKG2D receptor and its MICA and MICB ligands on tumor cells offers opportunities for therapeutic intervention. Interestingly, T cells and NK cells share several important inhibitory and activating receptors that can be targeted to enhance T cell- and NK cell-mediated immunity. These inhibitory receptor-ligand systems include CD161-CLEC2D, TIGIT-CD155, and NKG2A CD94-HLA-E. We also discuss emerging therapeutic strategies based on inhibitory and activating cytokines that profoundly impact the function of both lymphocyte populations within tumors.
ISSN:0732-0582
1545-3278
1545-3278
DOI:10.1146/annurev-immunol-101921-044122