Evidence map›Paper›PMID 31940590›Full record

ArticleJournal for immunotherapy of cancer2020

Non-thermal histotripsy tumor ablation promotes abscopal immune responses that enhance cancer immunotherapy.

Shibin Qu, Tejaswi Worlikar, Amy E Felsted, Anutosh Ganguly, Megan V Beems, Ryan Hubbard, Ashley L Pepple, Alicia A Kevelin, Hannah Garavaglia, Joe Dib and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
137citing papers in PubMed, 2 pooled it
8.6field-weighted citation impact, top 2% of its field
1 · What the graph read from it

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

137 citing papers in PubMed, 2 syntheses or guidelines pooled it, 204 citations in OpenAlex.

  1. Pooled it
  2. Histotripsy: the first noninvasive, non-ionizing, non-thermal ablation technique based on ultrasound.International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group · 2021
    Pooled it
  3. Trial
  4. Histotripsy for Liver Tumors: Breakthrough or Hype?Annals of surgical oncology · 2026
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77 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 2 countries.

Shibin Qu *Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Tejaswi Worlikar *Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Amy E Felsted *Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Anutosh GangulySurgery, University of Michigan, Ann Arbor, Michigan, USA.
Megan V BeemsSurgery, University of Michigan, Ann Arbor, Michigan, USA.
Ryan HubbardBiomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Ashley L PeppleSurgery, University of Michigan, Ann Arbor, Michigan, USA.
Alicia A KevelinSurgery, University of Michigan, Ann Arbor, Michigan, USA.
Hannah GaravagliaSurgery, University of Michigan, Ann Arbor, Michigan, USA.
Joe DibSurgery, University of Michigan, Ann Arbor, Michigan, USA.
Mariam TomaSurgery, University of Michigan, Ann Arbor, Michigan, USA.
Hai HuangSurgery, Ohio State University Medical Center, Columbus, Ohio, USA.
Allan TsungSurgery, Ohio State University Medical Center, Columbus, Ohio, USA.
Zhen XuBiomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Clifford Suhyun ChoSurgery, University of Michigan, Ann Arbor, Michigan, USA cliffcho@med.umich.edu.
University of Michigan–Ann Arbor · USThe Ohio State University Wexner Medical Center · USXijing Hospital · CN

Funding

UW Surgical Oncology Research Training Program (UW-SORT)T32CA090217 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Muhammed Murtaza, Heather B Neuman · 2001 to 2026
$8.3M
University of Michigan Surgical Oncology Research Training ProgramT32CA009672 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI JACQUELINE SARA JERUSS, WEIPING ZOU · 1991 to 2026
$6.0M
Novel, Noninvasive, Rapid Tumor Ablation Technology using HistotripsyR01CA211217 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI XU, ZHEN · 2018 to 2022
$2.7M
Re-engineering the tumor draining lymph node to achieve memory T cell-based adoptive immunotherapyI01BX001619 · VA · WM S. MIDDLETON MEMORIAL VETERANS HOSP · PI CHO, CLIFFORD · 2014 to 2022
–
BLRD VA I01 BX001619NCI NIH HHS R01 CA211217NCI NIH HHS T32 CA009672NCI NIH HHS T32 CA090217
6 · The paper itself

Abstract

backgroundDeveloping the ability to use tumor-directed therapies to trigger potentially therapeutic immune responses against cancer antigens remains a high priority for cancer immunotherapy. We hypothesized that histotripsy, a novel non-invasive, non-thermal ablation modality that uses ultrasound-generated acoustic cavitation to disrupt tissues, could engender adaptive immune responses to tumor antigens.

methodsImmunocompetent C57BL/6 mice inoculated with flank melanoma or hepatocellular carcinoma tumors were treated with histotripsy, thermal ablation, radiation therapy, or cytotoxic T lymphocyte-associated protein-4 (CTLA-4) blockade checkpoint inhibition. Lymphocyte responses were measured using flow cytometric and immunohistochemical analyses. The impact of histotripsy on abscopal immune responses was assessed in mice bearing bilateral tumors, or unilateral tumors with pulmonary tumors established via tail vein injection.

resultsHistotripsy ablation of subcutaneous murine melanoma tumors stimulated potent local intratumoral infiltration of innate and adaptive immune cell populations. The magnitude of this immunostimulation was stronger than that seen with tumor irradiation or thermal ablation. Histotripsy also promoted abscopal immune responses at untreated tumor sites and inhibited growth of pulmonary metastases. Histotripsy was capable of releasing tumor antigens with retained immunogenicity, and this immunostimulatory effect was associated with calreticulin translocation to the cellular membrane and local and systemic release of high mobility group box protein 1. Histotripsy ablation potentiated the efficacy of checkpoint inhibition immunotherapy in murine models of melanoma and hepatocellular carcinoma.

conclusionsThese preclinical observations suggest that non-invasive histotripsy ablation can be used to stimulate tumor-specific immune responses capable of magnifying the impact of checkpoint inhibition immunotherapy.

Indexed as

Ablation TechniquesAnimalsAntineoplastic Agents, ImmunologicalCombined Modality TherapyCTLA-4 AntigenHigh-Intensity Focused Ultrasound AblationLiver Neoplasms, ExperimentalLung NeoplasmsMelanoma, ExperimentalMiceMice, Inbred C57BLAntineoplastic Agents, ImmunologicalCTLA-4 AntigenCtla4 protein, mouseimmunologyoncologytumors

Identifiers

PMID31940590
PMCPMC7057529
OpenAlexW2999799781

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.