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Spatiotemporal local and abscopal cell death and immune responses to histotripsy focused ultrasound tumor ablation

ABSTRACT: Spatiotemporal local and abscopal cell death and immune responses to histotripsy focused ultrasound tumor ablation

PROVIDER: PRJNA914320 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22831000.fastq.gz	Fastqsanger.gz
	SRR22831100.fastq.gz	Fastqsanger.gz
	SRR22831001.fastq.gz	Fastqsanger.gz
	SRR22831101.fastq.gz	Fastqsanger.gz
	SRR22831002.fastq.gz	Fastqsanger.gz

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Spatiotemporal local and abscopal cell death and immune responses to histotripsy focused ultrasound tumor ablation

Project description:Histotripsy is a novel focused ultrasound tumor ablation modality with potent immunostimulatory effects. To measure the spatiotemporal kinetics of local and abscopal responses to histotripsy, C57BL/6 mice bearing bilateral flank B16 melanoma or Hepa1-6 hepatocellular carcinoma tumors were treated with unilateral sham or partial histotripsy. Treated and Controltralateral untreated (abscopal) tumors were analyzed using multicolor immunofluorescence, digital spatial profiling, RNA sequencing (RNASeq), and flow cytometry.

2023-01-12 | GSE221448 | GEO

Spatiotemporal local and abscopal cell death and immune responses to histotripsy focused ultrasound tumor ablation.

Project description:IntroductionHistotripsy is a novel focused ultrasound tumor ablation modality with potent immunostimulatory effects.MethodsTo measure the spatiotemporal kinetics of local andabscopal responses to histotripsy, C57BL/6 mice bearing bilateral flank B16 melanoma or Hepa1-6 hepatocellular carcinoma tumors were treated with unilateral sham or partial histotripsy. Treated and contralateral untreated (abscopal) tumors were analyzed using multicolor immunofluorescence, digital spatial profiling, RNA sequencing (RNASeq), and flow cytometry.ResultsUnilateral histotripsy triggered abscopal tumor growth inhibition. Within the ablation zone, early high mobility group box protein 1 (HMGB1) release and necroptosis were accompanied by immunogenic cell death transcriptional responses in tumor cells and innate immune activation transcriptional responses in infiltrating myeloid and natural killer (NK) cells. Delayed CD8+ T cell intratumoral infiltration was spatiotemporally aligned with cancer cell features of ferroptosis; this effect was enhanced by CTLA-4 blockade and recapitulated in vitro when tumor-draining lymph node CD8+ T cells were co-cultured with tumor cells. Inoculation with cell-free tumor fractions generated by histotripsy but not radiation or freeze/thaw conferred partial protection from tumor challenge.DiscussionWe propose that histotripsy may evoke local necroptotic immunogenic cell death, priming systemic adaptive immune responses and abscopal ferroptotic cancer cell death.

| S-EPMC9900174 | biostudies-literature

Transcriptomic profiling of diabetic rats treated with peripherical focused ultrasound (pFUS)

Project description:Transcriptomic profiling of diabetic rats treated with peripherical focused ultrasound (pFUS)

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Single-cell sequencing of brain macrophages after focused-ultrasound blood-brain barrier opening

Project description:Single-cell sequencing of brain macrophages after focused-ultrasound blood-brain barrier opening

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Microarray analysis of rat hippocampal microvessels at acute time points following focused ultrasound-induced increase in blood-brain barrier permeability

Project description:Therapeutic treatment options for central nervous system diseases are greatly limited by the blood-brain barrier (BBB). Focused ultrasound (FUS), in conjunction with circulating microbubbles, can be used to induce a targeted and transient increase in BBB permeability, providing a unique approach for the delivery of drugs from the systemic circulation into the brain. While preclinical research has demonstrated the utility of FUS, there remains a large gap in our knowledge regarding the impact of sonication on BBB gene expression. This work is focused on investigating the transcriptional changes in dorsal hippocampal rat microvessels in the acute stages following sonication. Microarray analysis of microvessels was performed at 6 and 24 hrs post-FUS. Microvessels were collected by laser capture microdissection. Relative gene expression was compared between samples collected from the sonicated hemisphere and samples collected from the hemisphere contralateral to sonication, as well as samples collected from rats not undergoing the FUS procedure.

2017-09-01 | E-MTAB-5251 | biostudies-arrayexpress

Single-cell sequencing of brain macrophages after focused-ultrasound blood-brain barrier opening

Project description:Focused Ultrasound (FUS) combined with microbubbles (FUS+MB) to transiently open the blood brain barrier (BBB) has shown promise as an immunotherapeutic in models of neurodegenerative disorders - resulting in significantly reduced pathological load and improved cognition. Preliminary histology and bulk tissue analysis of FUS+MB have indicated brain macrophage changes as a potential mechanism of the immunotherapy. However, prior to this study the temporal effect of FUS+MB on the two dominant brain macrophage populations - microglia and central nervous system associated macrophages (CAM) has not been reported. In this study, we establish that FUS+MB triggers a biphasic process involving both microglia and CAM. In the Phase I, 24h after treatment, microglia and resident CAM exhibit an early response signature, characterized by the upregulation of recruitment-associated chemokine and cytokines. In Phase II, 72h after treatment, CAM population size increases dramatically and both cell types exhibit a late response signature, characterized by upregulation of interferon genes indicative of cellular activation and immune response. Next, cell cycle analysis and immunohistochemistry indicate that microglia exhibit increased proliferation across both phases but CAM do not. Finally, the brain macrophage population size is correlated with the ultrasound-induced cavitation dose, indicating a dose-dependent response to treatment. The findings presented herein not only provide insight into the mechanism of the FUS+MB immunomodulatory effects but also into a mechanism of brain macrophage response that is capable of ameliorating neurological disease.

2023-06-17 | GSE198707 | GEO

Focused ultrasound ablation of melanoma with boiling histotripsy yields abscopal tumor control and antigen-dependent dendritic cell activation.

Project description:BackgroundBoiling histotripsy (BH), a mechanical focused ultrasound ablation strategy, can elicit intriguing signatures of anti-tumor immunity. However, the influence of BH on dendritic cell function is unknown, compromising our ability to optimally combine BH with immunotherapies to control metastatic disease.MethodsBH was applied using a sparse scan (1 mm spacing between sonications) protocol to B16F10-ZsGreen melanoma in bilateral and unilateral settings. Ipsilateral and contralateral tumor growth was measured. Flow cytometry was used to track ZsGreen antigen and assess how BH drives dendritic cell behavior.ResultsBH monotherapy elicited ipsilateral and abscopal tumor control in this highly aggressive model. Tumor antigen presence in immune cells in the tumor-draining lymph nodes (TDLNs) was ~3-fold greater at 24h after BH, but this abated by 96h. B cells, macrophages, monocytes, granulocytes, and both conventional dendritic cell subsets (i.e. cDC1s and cDC2s) acquired markedly more antigen with BH. BH drove activation of both cDC subsets, with activation being dependent upon tumor antigen acquisition. Our data also suggest that BH-liberated tumor antigen is complexed with damage-associated molecular patterns (DAMPs) and that cDCs do not traffic to the TDLN with antigen. Rather, they acquire antigen as it flows through afferent lymph vessels into the TDLN.ConclusionWhen applied with a sparse scan protocol, BH monotherapy elicits abscopal melanoma control and shapes dendritic cell function through several previously unappreciated mechanisms. These results offer new insight into how to best combine BH with immunotherapies for the treatment of metastatic melanoma.

| S-EPMC10508728 | biostudies-literature

Focused ultrasound ablation of melanoma with boiling histotripsy yields abscopal tumor control and antigen-dependent dendritic cell activation.

Project description:Background: Boiling histotripsy (BH), a mechanical focused ultrasound ablation strategy, can elicit intriguing signatures of anti-tumor immunity. However, the influence of BH on dendritic cell function is unknown, compromising our ability to optimally combine BH with immunotherapies to control metastatic disease. Methods: BH was applied using a sparse scan (1 mm spacing between sonications) protocol to B16F10-ZsGreen melanoma in bilateral and unilateral settings. Ipsilateral and contralateral tumor growth was measured. Flow cytometry was used to track ZsGreen antigen and assess how BH drives dendritic cell behavior. Results: BH monotherapy elicited ipsilateral and abscopal tumor control in this highly aggressive model. Tumor antigen presence in immune cells in the tumor-draining lymph nodes (TDLNs) was ~3-fold greater at 24h after BH, but this abated by 96h. B cells, macrophages, monocytes, granulocytes, and both conventional dendritic cell subsets (i.e. cDC1s and cDC2s) acquired markedly more antigen with BH. BH drove activation of both cDC subsets, with activation being dependent upon tumor antigen acquisition. Our data also suggest that BH-liberated tumor antigen is complexed with damage-associated molecular patterns (DAMPs) and that cDCs do not traffic to the TDLN with antigen. Rather, they acquire antigen as it flows through afferent lymph vessels into the TDLN. Conclusion: When applied with a sparse scan protocol, BH monotherapy elicits abscopal melanoma control and shapes dendritic cell function through several previously unappreciated mechanisms. These results offer new insight into how to best combine BH with immunotherapies for the treatment of metastatic melanoma.

| S-EPMC10879863 | biostudies-literature

Gene expression profie at single cell level of lung cells in healthy rats and rats with pulmonary hypertension treated with sham-stimulation or ultrasound

Project description:Focused ultrasound of the spleen is an emerging therapeutic modality and recent reports have shown efficacy in reducing inflammation. We used scRNA seq to identify the gene expression changes in lungs of healthy animals, animals with pulmonary hypertension treated with focused ultrasound of the spleen or sham stimulation.

2023-12-01 | GSE247625 | GEO

Immunomodulation of Intracranial Melanoma in Response to Blood-Tumor Barrier Opening with Focused Ultrasound - Bulk RNA seq

Project description:Immunomodulation of Intracranial Melanoma in Response to Blood-Tumor Barrier Opening with Focused Ultrasound - Bulk RNA seq

| PRJNA638393 | ENA