ArticleCancer cell2021
Stanniocalcin 1 is a phagocytosis checkpoint driving tumor immune resistance.
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Article in Cancer cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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97citing papers in PubMed
9.6field-weighted citation impact, top 1% of its field
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Who cites it
97 citing papers in PubMed, 150 citations in OpenAlex.
- Stanniocalcin-1 and -2: The insulin-like growth factor system and beyond.Molecular biology reports · 2026Review
- The prognostic value and molecular mechanisms ofTranslational cancer research · 2026Article
- STC1 is associated with tumor progression and suppressive niches in laryngeal squamous cell carcinoma.Translational cancer research · 2026Article
- Stanniocalcin 1 contributes to glioma stem cells phenotypic plasticity through NOTCH1/STAT3/GFPT2 axis.Oncogenesis · 2026Article
- Review
- Review
- Tescalcin is a phagocytic checkpoint driving immune escape and limiting immunotherapeutic efficacy in hepatocellular carcinoma.The Journal of clinical investigation · 2026Article
- Study on the anti-lung cancer effects of Gracillin from Reineckia carnea by targeting STC1.BMC cancer · 2026Article
- Immune Checkpoint Inhibitors and Immunomodulators for Cancer Immunotherapy: Insights Into Resistance and Therapeutic Strategies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Boosting immunogenic tumour cell death via nanotherapeutic targeting of the Stanniocalcin 1 phagocytosis checkpoint for enhanced cancer immunotherapy.Nature communications · 2026Article
- Therapy-induced remodeling of the tumor immune microenvironment: Mechanistic insights and implications for immunotherapy.Chinese medical journal · 2026Review
- Immunogenic cell death as a cornerstone for combination therapies with immune checkpoint blockade.Molecular cancer · 2026Review
- A novel role ofMicrobiology spectrum · 2026Article
- Molecular innate immune programs of tumor-associated macrophages in immune checkpoint blockade resistance: a staged framework from suppressive circuitry to translational bottlenecks.Frontiers in immunology · 2026Review
- Systematic Pan-Cancer Analysis of the Oncogenic and Immunological Function of Stanniocalcin-1 (STC1).Current medicinal chemistry · 2026Article
- Tumor-Derived CDC37 Inhibits Antigen Cross-Presentation in Dendritic Cells and Impairs Anti-Tumor Immunity in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Neutrophil extracellular traps-STC1 positive feedback loop promotes immune evasion and metastasis in bladder cancer.Journal for immunotherapy of cancer · 2025Article
- A novel tumor microenvironment-related gene signature for prognostic prediction of intrahepatic cholangiocarcinoma.Scientific reports · 2025Article
- Targeting tumor-intrinsic BCL9 reverses immunotherapy resistance by eliciting macrophage-mediated phagocytosis and antigen presentation.Nature communications · 2025Article
- Turning cold tumors into hot tumors to ignite immunotherapy.Molecular cancer · 2025Review
37 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 2 institutions in 1 country.
Heng LinDepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Ilona KryczekDepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Shasha LiDepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA; Department of Computational Medicine & Bioinformatics, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Michael D GreenCenter of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA; Department of Radiation Oncology and Veterans Affairs Ann Arbor Healthcare System, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Alicia AliDepartment of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Reema HamashaDepartment of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Shuang WeiDepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Linda VatanDepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Wojciech SzeligaDepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Sara GroveDepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Xiong LiDepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Jing LiDepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Weichao WangDepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Yijian YanDepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Jae Eun ChoiCenter of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA; Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Gaopeng LiDepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Yingjie BianDepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Ying XuDepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Jiajia ZhouDepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Jiali YuDepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Houjun XiaDepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Weimin WangDepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Ajjai AlvaDepartment of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Arul M ChinnaiyanDepartment of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI, USA; Department of Urology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Marcin CieslikDepartment of Computational Medicine & Bioinformatics, University of Michigan School of Medicine, Ann Arbor, MI, USA; Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Weiping ZouDepartment of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA; Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Graduate Program in Immunology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Graduate Program in Cancer Biology, University of Michigan School of Medicine, Ann Arbor, MI, USA. Electronic address: wzou@med.umich.edu.
University of Michigan · USHoward Hughes Medical Institute · US
Funding
XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI THEODORE S LAWRENCE · 1988 to 2026
$178.2MTissue/InformaticsP50CA186786 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Robert Timothy Dess · 2014 to 2026
$27.6MNaive T cells in Cancer Immune Evasion and ImmunotherapyR01CA217510 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZOU, WEIPING · 2017 to 2021
$3.3MMetabolic impact on T cell-mediated cancer immunity and therapyR01CA248430 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZOU, WEIPING · 2020 to 2024
$3.2MOvarian Cancer Epigenetics, Immunity and TherapyR01CA214911 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZOU, WEIPING · 2018 to 2022
$3.1MMDSCs in Ovarian CancerR01CA193136 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZOU, WEIPING · 2015 to 2019
$2.5MMemory T Cells in the Tumor MicroenvironmentR01CA152470 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZOU, WEIPING · 2011 to 2015
$1.9MHuman Tregs in Ovarian CancerR01CA099985 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZOU, WEIPING · 2006 to 2014
$1.8MNovel immunosupressive macrophages in human ovarian tumorR01CA123088 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZOU, WEIPING · 2007 to 2011
$1.4MNCI NIH HHS P30 CA046592NCI NIH HHS P50 CA186786NCI NIH HHS R01 CA099985NCI NIH HHS R01 CA123088NCI NIH HHS R01 CA152470NCI NIH HHS R01 CA193136NCI NIH HHS R01 CA214911NCI NIH HHS R01 CA217510NCI NIH HHS R01 CA248430
Abstract
Immunotherapy induces durable clinical responses in a fraction of patients with cancer. However, therapeutic resistance poses a major challenge to current immunotherapies. Here, we identify that expression of tumor stanniocalcin 1 (STC1) correlates with immunotherapy efficacy and is negatively associated with patient survival across diverse cancer types. Gain- and loss-of-function experiments demonstrate that tumor STC1 supports tumor progression and enables tumor resistance to checkpoint blockade in murine tumor models. Mechanistically, tumor STC1 interacts with calreticulin (CRT), an "eat-me" signal, and minimizes CRT membrane exposure, thereby abrogating membrane CRT-directed phagocytosis by antigen-presenting cells (APCs), including macrophages and dendritic cells. Consequently, this impairs APC capacity of antigen presentation and T cell activation. Thus, tumor STC1 inhibits APC phagocytosis and contributes to tumor immune evasion and immunotherapy resistance. We suggest that STC1 is a previously unappreciated phagocytosis checkpoint and targeting STC1 and its interaction with CRT may sensitize to cancer immunotherapy.
Indexed as
AnimalsAntigen PresentationGlycoproteinsImmunotherapyLymphocyte ActivationMacrophagesMicePhagocytosisReceptors, ImmunologicTumor EscapeGlycoproteinsReceptors, Immunologicteleocalcincalreticulincheckpointdendritic celleat-me signalmacrophagesPD-1phagocytosisstanniocalcin 1T cell immunitytumor
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