Tsc1, also known as Tuberous Sclerosis Complex 1, is an essential component of the pro-survival PI3K/AKT/MTOR signaling pathway. It plays a crucial role in processes such as development, cell growth, proliferation, survival, autophagy, and cilia development by interacting with various regulatory molecules. Tsc1 is a tumor suppressor gene, and its inactivation is associated with tuberous sclerosis complex (TSC), an autosomal dominant disorder [2].

In non-small cell lung cancer (NSCLC), a CRISPR screening in murine KrasG12D/Trp53-/-(KP) model identified Tsc1 as a potent regulator of programmed cell death ligand 1 (Pd-l1) expression in vitro and sensitivity to anti-programmed cell death receptor 1 (PD-1) treatment in vivo. Tsc1 knockout (KO) promoted the transcriptional and membrane expression of PD-L1 in cell lines. Patients with TSC1-mutant NSCLC receiving immune checkpoint blockade (ICB) had increased durable clinical benefit and survival, suggesting that Tsc1 loss defines a subtype of NSCLC with an inflamed tumor microenvironment and superior sensitivity to ICB [1].

In summary, Tsc1 is a key regulator in multiple biological processes, especially through its role in the PI3K/AKT/MTOR signaling pathway. The study of Tsc1 KO mouse models in NSCLC has revealed its significance in regulating tumor immunity and response to immunotherapy, providing valuable insights into the disease mechanism and potential treatment strategies for NSCLC [1,2].