ArticleNature medicine2021
Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination.
Registry-linked trialAbstract read
In one paragraph
Article in Nature medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06416436 (Immunotherapy in Combination With Ablative Radiosurgery to Ultra-high DoSes), which is not on this map. Cited by 662 papers, 5 of them syntheses that pooled it.
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0cells of the map it votes in
662citing papers in PubMed, 5 pooled it
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Immunotherapy in Combination With Ablative Radiosurgery to Ultra-high DoSes (ICARUS): A Phase I Dose-escalation Radiosurgery Study in Metastatic Cancers
Who cites it
662 citing papers in PubMed, 5 syntheses or guidelines pooled it.
- Hyperprogressive disease in carcinoma induced by immune checkpoint inhibitor therapy: a systematic review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Pooled it
- Antibody-Drug Conjugates for Locally Advanced and Metastatic Urothelial Carcinoma: A Systematic Review and Meta-Analysis.JAMA network open · 2026Pooled it
- Pooled it
- Efficacy of PD-1/PD-L1 inhibitors combined with multi-targeted anti-angiogenic TKIs in advanced or metastatic NSCLC: A meta-analysis based on RCTs.Frontiers in oncology · 2026Pooled it
- Impact of metastatic pattern and histologic subtype on PD-(L)1 inhibitor efficacy in HER2-negative advanced gastric and gastroesophageal cancer: a meta-analysis.Frontiers in oncology · 2026Pooled it
- Copanlisib in combination with nivolumab formicrosatellite stable colorectal cancer: a phase 1/2 trial.Nature communications · 2026Trial
- The anti-CD33 antibody drug conjugate gemtuzumab ozogamicin depletes and functionally resets CD33+ myeloid-derived suppressor cells in patients with metastatic cancer: a phase 2 single-arm, open-label trial.Journal of leukocyte biology · 2026Trial
- Sintilimab plus fruquintinib with or without radiotherapy for third-line treatment of colorectal cancer with liver metastases: study protocol for a randomized controlled, multicenter phase II trial.Frontiers in immunology · 2026Trial
- Final results of ANICCA-Class II, a single arm, open-label phase II trial assessing nivolumab in tissue-specific class II expressing metastatic microsatellite stable colorectal cancer, with a parallel assessment of the immunoscore-immune checkpoint as a predictive biomarker for single-agent anti-PD-1.Journal for immunotherapy of cancer · 2025Trial
- XL888 and pembrolizumab modulate the immune landscape of colorectal tumors in a phase Ib/II clinical trial.Oncoimmunology · 2025Trial
- Fruquintinib plus sintilimab in previously bevacizumab-treated, pMMR/MSS refractory metastatic colorectal cancer: a phase 2 clinical trial.Cancer immunology, immunotherapy : CII · 2025Trial
- Phase II Clinical Trial and Preclinical Evaluation of a Novel CD47 Blockade Combination in Refractory Microsatellite-Stable Metastatic Colorectal Cancer.Cancer research communications · 2025Trial
- Multicenter phase II trial of ipilimumab and nivolumab in metastatic or unresectable perivascular epithelioid cell tumor (PEComa): a substudy ofJournal for immunotherapy of cancer · 2025Trial
- Anlotinib plus sintilimab as first-line treatment for patients with advanced colorectal cancer (APICAL-CRC): an open-label, single-arm, phase II trial.Signal transduction and targeted therapy · 2025Trial
- Nivolumab and Relatlimab for the Treatment of Patients with Unresectable or Metastatic Mismatch Repair-Proficient Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Unlocking the therapeutic potential of immuno-radiotherapy: insights from preclinical and clinical research.Oncoimmunology · 2026Review
- Pooled analysis of 2 clinical trials of first-line chemoimmunotherapy for metastatic microsatellite stable colorectal cancer MEDITREME and METIMMOX studies.Oncoimmunology · 2026Article
- Lineage plasticity-driven immunometabolic state transitions in advanced prostate cancer: biomarkers and therapeutic stratification.Seminars in immunopathology · 2026Review
- ApolipoproteinEiScience · 2026Article
- Review
602 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
40 authors.
Jiali Yu *Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
Michael D Green *Center of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA. migr@med.umich.edu.ORCID http://orcid.org/0000-0003-4951-7118
Shasha LiDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Yilun SunDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-1341-382X
Sara N JourneyUniversity of Michigan Medical School, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-0987-9774
Jae Eun ChoiDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.
Syed Monem RizviChemical Engineering, University of Michigan, Ann Arbor, MI, USA.
Angel QinDivision of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Jessica J WaningerUniversity of Michigan Medical School, University of Michigan, Ann Arbor, MI, USA.
Xueting LangDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Zoey ChopraUniversity of Michigan Medical School, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-6349-2431
Issam El NaqaDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0001-6023-1132
Jiajia ZhouDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Yingjie BianDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-9599-9907
Long JiangCenter of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.
Alangoya TezelUniversity of Michigan Medical School, University of Michigan, Ann Arbor, MI, USA.
Jeremy SkvarceUniversity of Michigan Medical School, University of Michigan, Ann Arbor, MI, USA.
Rohan K AcharUniversity of Michigan Medical School, University of Michigan, Ann Arbor, MI, USA.
Merna SittoDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Benjamin S RosenDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Fengyun SuDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.
Sathiya P NarayananDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.
Xuhong CaoDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.
Shuang WeiDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Wojciech SzeligaDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Linda VatanDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Charles MayoDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Meredith A MorganDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Caitlin A SchonewolfDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Kyle CuneoDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Ilona KryczekDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-3130-2533
Vincent T MaDivision of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Christopher D LaoDivision of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Theodore S LawrenceDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Nithya RamnathVeterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI, USA.
Fei WenChemical Engineering, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0001-7970-4796
Arul M ChinnaiyanDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0001-9282-3415
Marcin CieslikDepartment of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
Ajjai AlvaCenter of Excellence for Cancer Immunology and Immunotherapy, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.
Weiping ZouDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA. wzou@med.umich.edu.ORCID http://orcid.org/0000-0001-7952-3549
Funding
XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI THEODORE S LAWRENCE · 1988 to 2026
$178.2MMICHIGAN MEDICAL SCIENTIST TRAINING PROGRAMT32GM007863 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI COLLINS, KATHLEEN L. · 1985 to 2024
$38.3MSequencing, Analysis, and Interpretation of SequencingUM1HG006508 · NHGRI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PIENTA, KENNETH J., ROBERTS, SCOTT · 2013 to 2016
$7.8MNaive 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
$3.1MSensitization to Chemoradiation by Therapeutic Targeting of the DNA Damage ResponseU01CA216449 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LAWRENCE, THEODORE S · 2017 to 2021
$3.0MMDSCs in Ovarian CancerR01CA193136 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZOU, WEIPING · 2015 to 2019
$2.5MOptimal Decision Making in Radiotherapy Using Panomics AnalyticsR01CA233487 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI EL NAQA, ISSAM M. · 2019 to 2023
$2.4MTargeting the DNA damage response in combination with radiation to induce innate immunity and improve immunotherapy efficacy in pancreatic cancerR01CA240515 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MORGAN, MEREDITH A · 2020 to 2024
$2.2MMemory 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
$1.8MNCI NIH HHS P30 CA046592NCI 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 CA233487NCI NIH HHS R01 CA240515NCI NIH HHS R01 CA248430NCI NIH HHS U01 CA216449NHGRI NIH HHS UM1 HG006508NIGMS NIH HHS T32 GM007863NIH HHS S10 OD020053NIH HHS S10 OD025046U-M | Comprehensive Cancer Center, University of Michigan (U-M Comprehensive Cancer Center) P30CA46592U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 1UM1HG006508U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA233487U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA240515U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA248430, CA217648, CA123088, CA099985, CA193136, CA152470U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) S10OD020053U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U01CA216440
Abstract
Metastasis is the primary cause of cancer mortality, and cancer frequently metastasizes to the liver. It is not clear whether liver immune tolerance mechanisms contribute to cancer outcomes. We report that liver metastases diminish immunotherapy efficacy systemically in patients and preclinical models. Patients with liver metastases derive limited benefit from immunotherapy independent of other established biomarkers of response. In multiple mouse models, we show that liver metastases siphon activated CD8
Indexed as
ImmunotherapyAnimalsCarcinoma, Non-Small-Cell LungCell Line, TumorCohort StudiesCombined Modality TherapyFemaleHumansLiver NeoplasmsLiver Neoplasms, ExperimentalLymphocyte ActivationMacrophagesMaleMelanomaMiceMice, Inbred C57BL
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Read underepoch 390
Registered trials
NCT06416436ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.