Checkpoint TIPE2 Limits the Helper Functions of NK Cells in Supporting Antitumor CD8+ T Cells. Issue 12 (19th February 2023)

• Record Type: Journal Article
• Authors: Bi, Jiacheng; Jin, Xiaomeng; Zheng, Chaoyue; Huang, Chen; Zhong, Chao; Zheng, Xiaohu; Tian, Zhigang; Sun, Haoyu
• Is Part Of: Advanced science. Volume 10:Issue 12(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-02-19
• Subjects: checkpoint inhibition -- natural killer cells -- Tbx21 -- Tnfaip8l2 -- tumor immunity; Science -- Periodicals; 505
• DOI: 10.1002/advs.202207499
• Languages: English
• ISSNs: 2198-3844

Abstract

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 : Natural killer (NK) cells are essential helpers for antitumor CD8 + T‐cell response. 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 antitumor CD8 + T cell response by promoting T‐bet/Eomes‐dependent NK cell effector functions.