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New checkpoint molecule for natural killer cell anti-tumor immunity revealed

TIPE2 expression of purified spleen NK cells from wild-type mice of Figure 1.2, 4, 6, or 10 weeks of age correlates with NK cell maturation in both mice and humans. Western blot. (B) UMAP of spleen NK cells of Pipe2WT / WT mice. The cells are color coded according to the defined subset. (C) Relative expression of the indicated genes in the subset defined from (B). (D) The relative expression level of Pipe2 was shown for the cluster in (B). (E) Pipe2 transcription levels of purified DX5- or DX5 + mouse liver NK cells or CD27SP, DP, or CD11bSP mouse bone marrow NK cells obtained from the dataset GSE43339 or the Immunological Genome Project database (www.immgen.org). Each. (F) TIPE2 expression in purified CD27 SP, DP, or CD11bSP spleen NK cells from wild-type mice was examined by Western blot. (G) tSNE of human peripheral blood NK cells. The cells are color coded according to the defined subset. (H) Relative expression of the indicated gene in the subset defined from (G). (I) The relative expression level of Pipe2 was shown for the cluster of (G). (J) Pipe2 transcription levels of purified CD56 bright or CD56 dimperipheral blood NK cells from healthy donors were obtained from dataset GSE79939 (61). (K) TIPE2 expression of purified CD56 bright or CD56dim peripheral blood NK cells from healthy donors was examined by Western blot. The (A, F, and K) data represent at least two independent experiments. Credit: DOI: 10.1126 / sciadv.abi6515

Immunotherapy is currently revolutionizing tumor treatment. However, most patients, especially those with solid tumors, do not benefit from available immunotherapy strategies due to their limited efficacy and safety.

Natural killer cells (NK cells) are cytotoxic innate immune cells that play an important role in immune surveillance against tumors. However, the underlying mechanism is still unknown.

Dr. Tian Zhigang’s group at the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences found that protein-8-like-2 (TIPE2) induced by tumor necrosis factor-α (TNF-α) is NK cell maturation. And anti-tumor immunity. This finding indicates that TIPE2 is a checkpoint molecule for NK cells and that targeting TIPE2 may be useful for NK-based tumor immunotherapy.

their study Was published in Science Advances September 15th.

Previous work by Dr. Tian’s group has already revealed the role of checkpoint receptor T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) and A3AR on NK cell function in tumor surveillance, tissue damage and regeneration. I am.

Based on these studies, they searched for checkpoint molecules during NK cell maturation, a process by which NK cells acquire optimal function.

Researchers performed single-cell transcriptional analysis of both human and mouse peripheral NK cells in a steady state. They found that human and mouse NK cells contained several subpopulations that correlated with the process of NK cell maturation from “immature” NK cells to “mature” NK cells. Importantly, TIPE2, a previously reported molecule that mediates immune tolerance, increased its expression as NK cells matured.

Researchers also investigated the role of this molecule in NK cell biology. They found that in NK-specific TIPE2-deficient mice, the levels of mature NK cells were elevated and NK cells showed enhanced effector function. This indicates that TIPE2 suppressed the functional maturation of NK cells.

In addition, NK-specific TIPE2-deficient mice showed better control of tumor growth in vivo with increased tumor infiltration of NK cells and enhanced effector function of tumor-infiltrated NK. cell..

These results suggest a promising approach to target TIPE2 for NK cell-based immunotherapy.


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For more information:
Jiacheng Bi et al, TIPE2 is a checkpoint for natural killer cell maturation and anti-tumor immunity. Science Advances (2021). DOI: 10.1126 / sciadv.abi6515

Quote: A new checkpoint molecule for anti-tumor immunity of natural killer cells has been revealed (October 15, 2021), https: //medicalxpress.com/news/2021-10-checkpoint-molecule-natural-killer-cell. Obtained from html on October 15, 2021

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New checkpoint molecule for natural killer cell anti-tumor immunity revealed

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