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Checkpoint TIPE2 Limits the Helper Functions of NK Cells in Supporting Antitumor CD8+ T Cells.
- Source :
- Advanced Science; 4/26/2023, Vol. 10 Issue 12, p1-10, 10p
- Publication Year :
- 2023
-
Abstract
- Natural killer (NK) cells not only are innate effector lymphocytes that directly participate in tumor surveillance but are also essential helpers in the antitumor CD8+ T‐cell response. However, the molecular mechanisms and potential checkpoints regulating NK cell helper functions remain elusive. Here, it is shown that the T‐bet/Eomes‐IFN‐γ axis in NK cells is essential for CD8+ T cell‐dependent tumor control, whereas T‐bet‐dependent NK cell effector functions are required for an optimal response to anti‐PD‐L1 immunotherapy. Importantly, NK cell‐expressed TIPE2 (tumor necrosis factor‐alpha‐induced protein‐8 like‐2) represents a checkpoint molecule for NK cell helper function, since Tipe2 deletion in NK cells not only enhances NK‐intrinsic antitumor activity but also indirectly improves the antitumor CD8+ T cell response by promoting T‐bet/Eomes‐dependent NK cell effector functions. These studies thus reveal TIPE2 as a checkpoint for NK cell helper function, whose targeting might boost the antitumor T cell response in addition to T cell‐based immunotherapy. [ABSTRACT FROM AUTHOR]
- Subjects :
- KILLER cells
T helper cells
T cells
CELL physiology
IMMUNE response
Subjects
Details
- Language :
- English
- ISSN :
- 21983844
- Volume :
- 10
- Issue :
- 12
- Database :
- Complementary Index
- Journal :
- Advanced Science
- Publication Type :
- Academic Journal
- Accession number :
- 163337132
- Full Text :
- https://doi.org/10.1002/advs.202207499