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. 2023 May 22;11(5):e005845. doi: 10.1136/jitc-2022-005845

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© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.

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iICPs in clinical trials. (A) iICPs participating in clinical trials have different action modes. PD-1 engagement activates SHP-2 and leads to repression of proximal signaling events. CBL-B and CISH ubiquitinate their respective targets: regulatory unit of PI3K and PLCγ1, leading to their inactivation. Finally, HPK1 phosphorylates SLP76 that recruits 14-3-3 proteins, following SLP-76 dissociation from LAT signalosome and leading to SLP-76 proteolysis. (B) These iICPs are involved in several clinical trials for cancer treatments. iICP, intracellular immune checkpoint.