{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:35:11Z","timestamp":1788449711193,"version":"build-2803163510"},"reference-count":22,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2022,2,4]]},"abstract":"<jats:p>\n                    Tuberous sclerosis complex subunit 1 (\n                    <jats:italic>TSC1<\/jats:italic>\n                    ) and 2 (\n                    <jats:italic>TSC2<\/jats:italic>\n                    ) are frequently mutated in non\u2013small cell lung cancer (NSCLC), however, their effects on antitumor immunity remained unexplored. A CRISPR screening in murine\n                    <jats:italic>\n                      Kras\n                      <jats:sup>G12D<\/jats:sup>\n                    <\/jats:italic>\n                    \/\n                    <jats:italic>\n                      Trp53\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    (KP) model identified\n                    <jats:italic>Tsc1<\/jats:italic>\n                    and\n                    <jats:italic>Tsc2<\/jats:italic>\n                    as potent regulators of programmed cell death ligand 1 (Pd-l1) expression in vitro and sensitivity to anti\u2013programmed cell death receptor 1 (PD-1) treatment in vivo.\n                    <jats:italic>TSC1<\/jats:italic>\n                    or\n                    <jats:italic>TSC2<\/jats:italic>\n                    knockout (KO) promoted the transcriptional and membrane expression of PD-L1 in cell lines.\n                    <jats:italic>TSC2<\/jats:italic>\n                    -deficient tumors manifested an inflamed microenvironment in patient samples and The Cancer Genome Atlas dataset. In syngeneic murine models, KP-\n                    <jats:italic>Tsc2<\/jats:italic>\n                    -KO tumors showed notable response to anti\u2013PD-1 antibody treatment, but\n                    <jats:italic>Tsc2<\/jats:italic>\n                    \u2013wild-type tumors did not. Patients with\n                    <jats:italic>TSC1<\/jats:italic>\n                    \/\n                    <jats:italic>TSC2<\/jats:italic>\n                    -mutant NSCLC receiving immune checkpoint blockade (ICB) had increased durable clinical benefit and survival. Collectively,\n                    <jats:italic>TSC1<\/jats:italic>\n                    \/\n                    <jats:italic>TSC2<\/jats:italic>\n                    loss defines a distinct subtype of NSCLC characterized as inflamed tumor microenvironment and superior sensitivity to ICB.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.abi9533","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T13:58:31Z","timestamp":1643983111000},"source":"Crossref","is-referenced-by-count":41,"title":["Loss of\n                    <i>TSC1\/TSC2<\/i>\n                    sensitizes immune checkpoint blockade in non\u2013small cell lung cancer"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4389-6188","authenticated-orcid":true,"given":"Qingyuan","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China."},{"name":"Institute of Thoracic Oncology, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6985-8959","authenticated-orcid":true,"given":"Hai","family":"Hu","sequence":"additional","affiliation":[{"name":"Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyuan","family":"Fang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhendong","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China."},{"name":"Institute of Thoracic Oncology, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4632-0512","authenticated-orcid":true,"given":"Guozhan","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China."},{"name":"Institute of Thoracic Oncology, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2892-6318","authenticated-orcid":true,"given":"Wai-Lung","family":"Ng","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong SAR, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2495-7504","authenticated-orcid":true,"given":"Alireza","family":"Khodadadi-Jamayran","sequence":"additional","affiliation":[{"name":"Applied Bioinformatics Laboratories and Genome Technology Center, Division of Advanced Research Technologies, New York University Langone Medical Center, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1725-7956","authenticated-orcid":true,"given":"Ting","family":"Chen","sequence":"additional","affiliation":[{"name":"Laura and Isaac Perlmutter Cancer Center, New York 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USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6731-5849","authenticated-orcid":true,"given":"Kristen","family":"Labbe","sequence":"additional","affiliation":[{"name":"Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Han","sequence":"additional","affiliation":[{"name":"Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Geng","sequence":"additional","affiliation":[{"name":"Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, 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