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Cited by 140Cancer Immunotherapy and BiomarkersAutophagy in Disease and TherapyImmunotherapy and Immune Responses

ULK1 inhibition overcomes compromised antigen presentation and restores antitumor immunity in LKB1-mutant lung cancer

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Deng, Jiehui, Thennavan, Aatish, Dolgalev, Igor, Chen, Ting, Li, Jie, Marzio, Antonio, Poirier, John T., Peng, David H. +30 more·2021·Nature Cancer
DOI 10.1038/s43018-021-00208-6PMC PMC8205437
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  • STK11-mutant tumors are characterized by low levels of antigen presentation compared with tumors wild-type for STK11.

    “STK11-mutant tumors are characterized by lower T-cell infiltration (1, 7, 8), higher levels of immune-suppressive neutrophils (8), and low levels of antigen presentation (9, 10) compared with those wild-type for STK11, contributing to their immune evasive phenotype.”

    From TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i> -Mutant Tumors to Anti–PD-1 Immunotherapy (2025) · cites this paper as [9]

    In “LKB1 loss suppresses antigen presentation” (page not supplied), the paper reports reduced expression of antigen-processing and presentation machinery in STK11/LKB1-mutant lung adenocarcinomas compared with tumors without that mutation. The comparison is specifically between TP53-mutant tumors with and without a co-occurring STK11/LKB1 mutation; it does not establish the claim for tumors generally. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • KL and KP cell lines were authenticated using PCR and Western blotting as previously published.

    “Both KL and KP cells were authenticated using PCR and Western blotting, as previously published (9)”

    From TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i> -Mutant Tumors to Anti–PD-1 Immunotherapy (2025) · cites this paper as [9]

    The Methods > Cell lines section (page unavailable) says that KL and KP Ulk1 shRNA stable cell lines were generated and that selected stable lines were validated by western blot. It does not say that both KL and KP cells were authenticated by PCR and Western blotting; the PCR described elsewhere in Methods concerns other procedures, not cell authentication. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Previous work has shown that STK11-mutant tumors have impaired antigen presentation, characterized by reduced expression of genes related to neoantigen processing and presentation.

    “Previous work has shown that STK11-mutant tumors have impaired antigen presentation, characterized by reduced expression of genes related to neoantigen processing and presentation (9).”

    From TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i> -Mutant Tumors to Anti–PD-1 Immunotherapy (2025) · cites this paper as [9]

  • The KL GEMM is highly resistant to anti-PD-1 therapy.

    “Consistent with STK11-deficient human tumors, this lung tumor model is highly resistant to anti–PD-1 therapy (9, 19).”

    From TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i> -Mutant Tumors to Anti–PD-1 Immunotherapy (2025) · cites this paper as [9]

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Cited by

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Authors
Deng, J., Thennavan, A., Dolgalev, I., Chen, T., Li, J., Marzio, A., Poirier, J. T., Peng, D. H., Bulatovic, M., Mukhopadhyay, S., Silver, H., Papadopoulos, E., Pyon, V., Thakurdin, C., Han, H., Li, F., Li, S., Ding, H., Hu, H., Pan, Y., Weerasekara, V., Jiang, B., Wang, E. S., Ahearn, I., Philips, M., Papagiannakopoulos, T., Tsirigos, A., Rothenberg, E., Gainor, J., Freeman, G. J., Rudin, C. M., Gray, N. S., Hammerman, P. S., Pagano, M., Heymach, J. V., Perou, C. M., Bardeesy, N., & Wong, K.-K.
Affiliations
  • NYU Langone Health (US)
  • University of North Carolina at Chapel Hill (US)
  • Memorial Sloan Kettering Cancer Center (US)
  • NYU Langone’s Laura and Isaac Perlmutter Cancer Center (US)
  • Harvard University (US)
  • New York University (US)
  • Massachusetts General Hospital (US)
  • Stanford Medicine (US)
  • Howard Hughes Medical Institute (US)
  • The University of Texas MD Anderson Cancer Center (US)
Corresponding author
Wong, Kwok-Kin
ORCID
Venue
Nature Cancer
Publisher
Springer Science and Business Media LLC
Published
2021-05-17
Volume
2
Issue
5
Pages
503-514
ISSN
2662-1347 (ISSN-L)
DOI
10.1038/s43018-021-00208-6
PMC
PMC8205437
OpenAlex
W3162565798
Cited by
140
References
8
Citations by year
2026: 15 · 2025: 26 · 2024: 26 · 2023: 35 · 2022: 24 · 2021: 14
FWCI
9.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Cancer (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • UNC Libraries
Funders
U.S. Department of Health & Human Services | NIH | National Cancer Institute (T32 CA009161, R01CA76584, SPORE CA058223, R01CA219670)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
non-small cell lung cancer, antigen processing and presentation, immunoproteasome, autophagy inhibition, anti-PD-1 therapy, tumor mutational burden, antitumor immunity, effector T cell expansion, combination immunotherapy
MeSH terms
Autophagy-Related Protein-1 Homolog, Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Antigen Presentation, Intracellular Signaling Peptides and Proteins

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