ArticleMolecular cancer therapeutics2022
Reverse Translating Molecular Determinants of Anti-Programmed Death 1 Immunotherapy Response in Mouse Syngeneic Tumor Models.
Article in Molecular cancer therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- HDAC inhibitor GCJ-490A modulates tumor microenvironment and synergizes with PD-1 antibody against breast and lung cancers in syngeneic murine models.Acta pharmacologica Sinica · 2026Article
- Influence of immune checkpoint inhibitor target and timing on combination treatment with antibody-based β-emitting targeted radionuclide therapy across tumor immunogenicity profiles.Frontiers in immunology · 2026Article
- Highly selective HPK1 inhibitor NDI-101150 mediates immune cell activation and robust antitumor responses, distinct from immune checkpoint blockade.Journal for immunotherapy of cancer · 2025Article
- Augment proteasome inhibitor efficacy activates CD8Cell reports. Medicine · 2025Article
- Acasunlimab, an Fc-inert PD-L1×4-1BB bispecific antibody, combined with PD-1 blockade potentiates antitumor immunity via complementary immune modulatory effects.Journal for immunotherapy of cancer · 2025Article
- Lenvatinib enhances antitumor immunity of anti-PD-1 antibody.International journal of clinical oncology · 2025Review
- Development of a Microvessel Density Gene Signature and Its Application in Precision Medicine.Cancer research communications · 2025Article
- IL-27 elicits a cytotoxic CD8Nature · 2025Article
- Exploiting temporal aspects of cancer immunotherapy.Nature reviews. Cancer · 2024Review
- MDM2/MDMX inhibition by Sulanemadlin synergizes with anti-Programmed Death 1 immunotherapy in wild-type p53 tumors.iScience · 2024Article
- Conserved immuno-collagenic subtypes predict response to immune checkpoint blockade.Cancer communications (London, England) · 2024Article
- Tretinoin improves the anti-cancer response to cyclophosphamide, in a model-selective manner.BMC cancer · 2024Article
- High B7-H3 expression with low PD-L1 expression identifies armored-cold tumors in triple-negative breast cancer.NPJ breast cancer · 2024Article
- Tumor cell-intrinsic PD-1 promotes Merkel cell carcinoma growth by activating downstream mTOR-mitochondrial ROS signaling.Science advances · 2024Article
- Antitumor effect of anti-vascular therapy with STING agonist depends on the tumor microenvironment context.Frontiers in oncology · 2023Article
- TYRO3 blockade enhances anti-PD-1 therapy response by modulating expression of CCN1 in tumor microenvironment.Journal for immunotherapy of cancer · 2023Article
- Preclinical characterization and clinical translation of pharmacodynamic markers for MK-5890: a human CD27 activating antibody for cancer immunotherapy.Journal for immunotherapy of cancer · 2022Article
- Distinct antibody clones detect PD-1 checkpoint expression and block PD-L1 interactions on live murine melanoma cells.Scientific reports · 2022Article
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29 authors.
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Abstract
Targeting the programmed death 1/programmed death ligand 1 (PD-1/PD-L1) pathway with immunotherapy has revolutionized the treatment of many cancers. Somatic tumor mutational burden (TMB) and T-cell-inflamed gene expression profile (GEP) are clinically validated pan-tumor genomic biomarkers that can predict responsiveness to anti-PD-1/PD-L1 monotherapy in many tumor types. We analyzed the association between these biomarkers and the efficacy of PD-1 inhibitor in 11 commonly used preclinical syngeneic tumor mouse models using murinized rat anti-mouse PD-1 DX400 antibody muDX400, a surrogate for pembrolizumab. Response to muDX400 treatment was broadly classified into three categories: highly responsive, partially responsive, and intrinsically resistant to therapy. Molecular and cellular profiling validated differences in immune cell infiltration and activation in the tumor microenvironment of muDX400-responsive tumors. Baseline and on-treatment genomic analysis showed an association between TMB, murine T-cell-inflamed gene expression profile (murine-GEP), and response to muDX400 treatment. We extended our analysis to investigate a canonical set of cancer and immune biology-related gene signatures, including signatures of angiogenesis, myeloid-derived suppressor cells, and stromal/epithelial-to-mesenchymal transition/TGFβ biology previously shown to be inversely associated with the clinical efficacy of immune checkpoint blockade. Finally, we evaluated the association between murine-GEP and preclinical efficacy with standard-of-care chemotherapy or antiangiogenic agents that previously demonstrated promising clinical activity, in combination with muDX400. Our profiling studies begin to elucidate the underlying biological mechanisms of response and resistance to PD-1/PD-L1 blockade represented by these models, thereby providing insight into which models are most appropriate for the evaluation of orthogonal combination strategies.
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