Leucine rich repeats and calponin homology domain containing 1 inhibits NK-92 cell cytotoxicity through attenuating Src signaling

Kai Dai, Zubing Chen, Sha She, Jinzhi Shi, Jiling Zhu, Yabing Huang
Immunobiology 2020 March 9, : 151934
NK-92 cell line has been used as anti-tumor cytotoxic effector cells in immunotherapy. Leucine-rich repeats and calponin homology domain containing 1 (LRCH1) is a novel gene of which the function is unclear. In the present study, we investigated the role of LRCH1 in NK-92 cell cytotoxicity. LRCH1 was ablated in NK-92 cells through CRISP-Cas9-mediated knockout. LRCH1 knockout did not influence the basal behavior of NK-92 cells such as cell survival, expression of natural cytotoxicity receptors, and proliferation. However, upon the contact with tumor cells, LRCH1 knockout promoted NK-92 cell cytotoxicity to tumor cells. Besides, LRCH1 knockout increased the production of cytotoxic mediators such as IFN-γ, TNF-α, IL-2, and granzyme B in NK-92 cells after tumor cell contact. Similarly, LRCH1 knockout increased the production of cytokines and granzyme B upon NKp30 engagement. Further experiments revealed that LRCH1 knockout enhanced the activation of Src and Lck kinase which are important for natural killer cell cytotoxicity. The in vivo assay confirmed the up-regulation of the tumoricidal activity of LRCH1-/- NK-92 cells, as demonstrated by more robust tumor cell killing. Importantly, human primary natural killer cells exhibited a similar increase in the production of IFN-γ and TNF-α when LRCH1 was knocked out. In conclusion, our study revealed the role of LRCH1 as a negative regulator of NK-92 cell cytotoxicity.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"