{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Skoulidis F"],"funding":["NCATS NIH HHS","NCI NIH HHS","NIH HHS"],"pagination":["462-471"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11560846"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["635(8038)"],"pubmed_abstract":["For patients with advanced non-small-cell lung cancer (NSCLC), dual immune checkpoint blockade (ICB) with CTLA4 inhibitors and PD-1 or PD-L1 inhibitors (hereafter, PD-(L)1 inhibitors) is associated with higher rates of anti-tumour activity and immune-related toxicities, when compared with treatment with PD-(L)1 inhibitors alone. However, there are currently no validated biomarkers to identify which patients will benefit from dual ICB<sup>1,2</sup>. Here we show that patients with NSCLC who have mutations in the STK11 and/or KEAP1 tumour suppressor genes derived clinical benefit from dual ICB with the PD-L1 inhibitor durvalumab and the CTLA4 inhibitor tremelimumab, but not from durvalumab alone, when added to chemotherapy in the randomized phase III POSEIDON trial<sup>3</sup>. Unbiased gene"],"journal":["Nature"],"pubmed_title":["CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors."],"pmcid":["PMC11560846"],"funding_grant_id":["P30 CA016058","S10 OD024977","R01 CA276917","P30 CA016672","P50 CA070907","P30 CA016042","R01 CA279452","P30 CA008748","T32 CA009172","R01 CA205150","UL1 TR001863","R01 CA262469"],"pubmed_authors":["Carbone DP","Johnson ML","Murray JC","Killam J","Zhang J","Garassino MC","Gray JE","Elamin YY","Poteete A","Hellmann MD","Venkatraman D","Byers LA","Herbst RS","Heymach JV","Pecot CV","Shaish H","Araujo HA","Montesion M","Scheffler M","Digumarthy S","Janne PA","Katz S","Awad MM","Winslow MM","Marrone KA","Gay C","Juan JM","Mezquita L","Tsao A","Scagliotti GV","Planchard D","Goldberg SB","Lau SCM","Lee R","Garon EB","Zhu Z","Galan-Cobo A","Jahchan N","Levy B","Hellyer JA","Mooradian MJ","Behrens C","Shu CA","Blumenschein GR","Ritterhouse L","Besse B","Yu Y","Bivona TG","Lam VK","Molkentine D","Wistuba II","Dimou A","Schalper K","Stewart R","Kemp HN","Zhou T","Swisher S","Cascone T","Le JT","Forde PM","Stewart T","Blakely CM","Ni Y","Rizvi NA","Qian Y","Mann H","Davies KD","Schmidt ST","Gandara DR","Rudin CM","Negrao MV","Kong Y","Takehara T","Leighl NB","Marmarelis ME","Gibbons DL","Carter B","Tabbo F","Owen DH","Rosen MJ","Wakelee HA","Memmott R","Peters S","Anagnostou V","Lee JJ","Gainor JF","Cummings AL","Bestvina CM","Huang A","Segal J","Roth JA","Shaw AT","Brahmer JR","Azok JT","Sun X","Johnson RP","Riess JW","Woodcock MG","Ricciuti B","Aggarwal C","Le X","Camidge DR","Winters IP","Min C","Albacker L","Sacher AG","Lacroix L","Arbour KC","Wong KK","Do MT","Walther Z","Goldman JW","Saltos AN","Papadimitrakopoulou VA","Skoulidis F","Van Allen EM","Wolf J","Vokes N","Pan X","Neal JW","Palmer R","Kier M","Patil PD","Parra Cuentas ER","Paula AG","Lai Z","Jewsbury P","Rotow J","Liu C","Lewis WE","Pennell NA"],"additional_accession":[]},"is_claimable":false,"name":"CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors.","description":"For patients with advanced non-small-cell lung cancer (NSCLC), dual immune checkpoint blockade (ICB) with CTLA4 inhibitors and PD-1 or PD-L1 inhibitors (hereafter, PD-(L)1 inhibitors) is associated with higher rates of anti-tumour activity and immune-related toxicities, when compared with treatment with PD-(L)1 inhibitors alone. However, there are currently no validated biomarkers to identify which patients will benefit from dual ICB<sup>1,2</sup>. Here we show that patients with NSCLC who have mutations in the STK11 and/or KEAP1 tumour suppressor genes derived clinical benefit from dual ICB with the PD-L1 inhibitor durvalumab and the CTLA4 inhibitor tremelimumab, but not from durvalumab alone, when added to chemotherapy in the randomized phase III POSEIDON trial<sup>3</sup>. Unbiased gene","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Nov","modification":"2026-06-01T17:41:45.011Z","creation":"2025-04-04T02:46:50.569Z"},"accession":"S-EPMC11560846","cross_references":{"pubmed":["39385035"],"doi":["10.1038/s41586-024-07943-7"]}}