1c:I[776865,["/_next/static/chunks/bb923814e1f4d2e9.js","/_next/static/chunks/dd3ee9f5b7716ca6.js","/_next/static/chunks/4204a0ae82542ca8.js","/_next/static/chunks/30036bedc5269936.js","/_next/static/chunks/6e1aa89a642f40be.js","/_next/static/chunks/cd5e572bc3e4eb92.js","/_next/static/chunks/8ffd0b71567920d8.js","/_next/static/chunks/67ea6dfd21f16c5f.js","/_next/static/chunks/24eb4379f68013fd.js","/_next/static/chunks/b8cd775ffdf935bd.js","/_next/static/chunks/983103cd9eb7b428.js","/_next/static/chunks/d4ac9dcf27f6ff52.js","/_next/static/chunks/294b9525248c8e5f.js"],"Grid"] 1d:I[617291,["/_next/static/chunks/bb923814e1f4d2e9.js","/_next/static/chunks/dd3ee9f5b7716ca6.js","/_next/static/chunks/4204a0ae82542ca8.js","/_next/static/chunks/30036bedc5269936.js","/_next/static/chunks/6e1aa89a642f40be.js","/_next/static/chunks/cd5e572bc3e4eb92.js","/_next/static/chunks/8ffd0b71567920d8.js","/_next/static/chunks/67ea6dfd21f16c5f.js","/_next/static/chunks/24eb4379f68013fd.js","/_next/static/chunks/b8cd775ffdf935bd.js","/_next/static/chunks/983103cd9eb7b428.js","/_next/static/chunks/d4ac9dcf27f6ff52.js","/_next/static/chunks/294b9525248c8e5f.js"],"GridCol"] 1e:I[734616,["/_next/static/chunks/bb923814e1f4d2e9.js","/_next/static/chunks/dd3ee9f5b7716ca6.js","/_next/static/chunks/4204a0ae82542ca8.js","/_next/static/chunks/30036bedc5269936.js","/_next/static/chunks/6e1aa89a642f40be.js","/_next/static/chunks/cd5e572bc3e4eb92.js","/_next/static/chunks/8ffd0b71567920d8.js","/_next/static/chunks/67ea6dfd21f16c5f.js","/_next/static/chunks/24eb4379f68013fd.js","/_next/static/chunks/b8cd775ffdf935bd.js","/_next/static/chunks/983103cd9eb7b428.js","/_next/static/chunks/d4ac9dcf27f6ff52.js","/_next/static/chunks/294b9525248c8e5f.js"],"Avatar"] 1f:I[432972,["/_next/static/chunks/bb923814e1f4d2e9.js","/_next/static/chunks/dd3ee9f5b7716ca6.js","/_next/static/chunks/4204a0ae82542ca8.js","/_next/static/chunks/30036bedc5269936.js","/_next/static/chunks/6e1aa89a642f40be.js","/_next/static/chunks/cd5e572bc3e4eb92.js","/_next/static/chunks/8ffd0b71567920d8.js","/_next/static/chunks/67ea6dfd21f16c5f.js","/_next/static/chunks/24eb4379f68013fd.js","/_next/static/chunks/b8cd775ffdf935bd.js","/_next/static/chunks/983103cd9eb7b428.js","/_next/static/chunks/d4ac9dcf27f6ff52.js","/_next/static/chunks/294b9525248c8e5f.js"],"default"] 20:T4b0,Tuberous sclerosis complex subunit 1 (TSC1) and 2 (TSC2) are frequently mutated in non-small cell lung cancer (NSCLC), however, their effects on antitumor immunity remained unexplored. A CRISPR screening in murine Kras^G12D/Trp53^-/- (KP) model identified Tsc1 and Tsc2 as potent regulators 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 or TSC2 knockout (KO) promoted the transcriptional and membrane expression of PD-L1 in cell lines. TSC2-deficient tumors manifested an inflamed microenvironment in patient samples and The Cancer Genome Atlas dataset. In syngeneic murine models, KP-Tsc2-KO tumors showed notable response to anti-PD-1 antibody treatment, but Tsc2-wild-type tumors did not. Patients with TSC1/TSC2-mutant NSCLC receiving immune checkpoint blockade (ICB) had increased durable clinical benefit and survival. Collectively, TSC1/TSC2 loss defines a distinct subtype of NSCLC characterized as inflamed tumor microenvironment and superior sensitivity to ICB.

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