Quantitative MRI cell tracking of immune cell recruitment to tumors and draining lymph nodes in response to anti-PD-1 and a DPX-based immunotherapy

Tremblay, Marie-Laurence; O’Brien-Moran, Zoe; Rioux, James A.; Nuschke, Andrea; Davis, Christa; Kast, W. Martin; Weir, Genevieve; Stanford, Marianne M.; Brewer, Kimberly

doi:10.1080/2162402x.2020.1851539

Cited by 7 publications

(6 citation statements)

References 36 publications

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“…The smallest immune cells (5-7µm), CD8 + T cells, which also have lower phagocytic activity, had much lower iron loading when labelled with MEs (0.22-0.3pg/cell, both MLRs) compared to SPIO (3pg). These results correspond well with other literature indicating average cell loading of 3-5pg iron/cell when using SPIO 9,30 . This level of iron loading in the MEs is typically on the low end of detectability in MRI cell tracking (ideally > 0.5pg/cell) indicating that MEs may not be an optimal choice for this cell type, or that if they are used, more invasive methods of labelling may be necessary, such as transporation and transfection agents.…”

Section: Discussionsupporting

confidence: 92%

“…The number of SPIO-labelled MDSCs was stable over the 8-day period (Fig. 5a), which is consistent with SPIO degradation rates seen anecdotally in our lab and in previous studies 9,10 . Interestingly, the number of MElabelled MDSCs was also stable over time and consistently higher than the number of SPIO-labelled MDSCs present.…”

Section: In Vivo Tracking Of Me-labelled Mdscssupporting

confidence: 90%

“…SPIO-labelled cell tracking with MRI is a powerful technique that can provide 3D resolution of therapy location in tandem with rich anatomical details of disease progression, such as tumour size, shape, and metastases. The applications of SPIO MRI contrast agents are broad -through in vivo tracking of tumours [4][5][6][7] , therapies 8 , immune cells [9][10][11][12][13] and vaccines 14 , as well as other uses, they can serve as valuable tools in the early detection of disease and the study of disease mechanisms and progression.…”

Section: Introduction Page 3/23mentioning

confidence: 99%

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Use of Magnetotactic Bacteria as an MRI Contrast Agent for In Vivo Tracking of Adoptively Transferred Immune Cells

Nuschke,

Sobey-Skelton,

Dawod

et al. 2023

Mol Imaging Biol

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In vivo immune cell tracking using MRI is a valuable tool for studying the mechanisms underlying successful cancer therapies. Current cell labeling methods using superparamagnetic iron oxide (SPIO) lack the speci city and persistence needed to track the fate and location of transplanted cells long-term. Magnetospirillium magneticum is a commercially available, iron-producing bacterium that can be taken up by, and live harmoniously within, mammalian cells as magneto-endosymbionts (MEs). MEs have shown promise as labeling agents for in vivo stem and cancer cell tracking but have yet to be evaluated in immune cells. This pilot study examined ME labeling in myeloid-derived suppressor cells (MDSCs), cytotoxic T lymphocytes (CTLs) and dendritic cells (DCs) and its effects on cell purity, function and MRI contrast. Procedures:MDSCs, CTLs and DCs were incubated with MEs at various ME labelling ratios (MLR) and various biological metrics and iron uptake were assessed. For in vivo imaging, MDSCs were labeled overnight with either MEs or SPIO (Molday ION Rhodamine B) and injected into C3 tumor-bearing mice via tail vein injection 24 days post-implant and scanned daily with MRI for one week to assess cellular quanti cation. ResultsFollowing incubations MDSCs contained 0.62 and 2.22 pg Fe/ cell. CTLs achieved Fe loading of < 0.5 pg/ cell and DCs achieved Fe loading of ~ 1.4pg/cell. The suppressive functionality of MDSCs at 1000MLR was not affected by ME labeling but was affected at 2000MLR. Markers of CTL dysfunction were not markedly affected by ME labeling, nor were DC markers. In vivo data demonstrated that the MDSCs labeled with MEs generated su cient contrast to be detectable using TurboSPI, similar to SPIO-labeled cells. ConclusionsCells can be labeled with pre-clinically relevant amounts of MEs without compromising cell viability. Care must be taken at higher concentrations of MEs, which may affect the functional activity and/or morphology of some cell types. Immune cells with minimal phagocytic behaviour have much lower iron content per cells after incubation with MEs vs SPIO; however, MEs can successfully be used as a contrast agent for phagocytic immune cells.

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Section: Discussionsupporting

confidence: 92%

Section: In Vivo Tracking Of Me-labelled Mdscssupporting

confidence: 90%

Section: Introduction Page 3/23mentioning

confidence: 99%

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Use of Magnetotactic Bacteria as an MRI Contrast Agent for In Vivo Tracking of Adoptively Transferred Immune Cells

Nuschke,

Sobey-Skelton,

Dawod

et al. 2023

Mol Imaging Biol

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“…In addition, immunotherapy has been manifested to gradually become an integral component of cancer therapy [ 13 ]. Studies have revealed that analysing the characteristics of TME, especially immune cell infiltration, can improve the understanding of the likelihood of immunotherapeutic response or survival [ 14 ]. In recent years, owing to the emergence of novel immunotherapy strategies involving PD-1 and PD-L1 and the clinical efficacy of PD-1 and PD-L1 blockade in various solid cancers, blocking of the PD-1 and PD-L1 pathways has emerged as an effective strategy for cancer treatment [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

HAUS Augmin-Like Complex Subunit 1 Influences Tumour Microenvironment and Prognostic Outcomes in Glioma

Yao

et al. 2022

Journal of Oncology

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Background. The expression of HAUS Augmin-like complex subunit 1 (HAUS1), a protein-coding gene, is low in normal samples among various cancers with pan-cancer analysis. The depletion of HAUS1 in cells decreases the G2/M cell compartment and induces apoptosis. However, the detailed expression pattern of HAUS1 and its correlation with immune infiltration in glioma (LGG and GBM) (LGG: low-grade glioma; GBM: glioblastoma) remain unknown. Therefore, in this study, we examined the role and prognostic value of HAUS1 in glioma. Methods. Transcriptional expression data of HAUS1 were collected from the CGGA and TCGA databases. The Kaplan–Meier analysis, univariate and multivariate Cox analyses, and receiver operating characteristic (ROC) curves were used to analyse the clinical significance of HAUS1 in glioma. The STRING database was used to analyse protein-protein interactions (PPI), and the “ClusterProfiler” package was used for functional enrichment analysis to examine the possible biological roles of HAUS1. In addition, the HAUS1 promoter methylation modification was analysed using MEXPRESS, and the association between HAUS1 expression and tumour-infiltrating immune cells was investigated using CIBERSORT. Results. Based on the data retrieved from TCGA (703 samples) and CGGA (1018 samples), an elevated expression of HAUS1 was observed in glioma samples, which was associated with poorer survival of patients, unfavourable clinical characteristics, 1p/19q codeletion status, WHO grade, and IDH mutation status. Furthermore, multivariate and univariate Cox analyses revealed that HAUS1 was an independent predictor of glioma. HAUS1 expression level was associated with several tumour-infiltrating immune cells, such as Th2 cells, macrophages, and activated dendritic cells. The outcomes of ROC curve analysis showed that HAUS1 was good to prognosticate immune infiltrating levels in glioma with a higher area under the curve (AUC) value (AUC = 0.974). Conclusions. HAUS1 was upregulated and served as a biomarker for poor prognosis in patients with glioma. High HAUS1 expression was associated with several tumour-infiltrating immune cells such as Th2 cells, macrophages, and activated dendritic cells, which had high infiltration levels. Therefore, these findings suggest that HAUS1 is a potential biomarker for predicting the prognosis of patients with glioma and plays a pivotal role in immune infiltration in glioma.

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“…Tremblay et al used MRI technology to quantitatively track cytotoxic T lymphocytes (CTLs) and myeloid cells (MLCs) labeled with superparamagnetic iron oxide nanoparticles (SPIO) in vitro. 75 The results showed that these quantitative molecular MRI techniques can be extended to the study of various cancers and immunotherapy combinations, thereby deepening the understanding of longitudinal immunological changes and their mechanisms. Dekaban et al reviewed the use of MRI technology to track the migration of dendritic cells (DCs) labeled with iron oxide nanoparticles in vitro.…”

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confidence: 99%

Cancer Immunotherapy and Medical Imaging Research Trends from 2003 to 2023: A Bibliometric Analysis

Tang,

Fan,

Wang

et al. 2024

JMDH

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With the rapid development of immunotherapy, cancer treatment has entered a new phase. Medical imaging, as a primary diagnostic method, is closely related to cancer immunotherapy. However, until now, there has been no systematic bibliometric analysis of the state of this field. Therefore, the main purpose of this article is to clarify the past research trajectory, summarize current research hotspots, reveal dynamic scientific developments, and explore future research directions. Patients and Methods: A comprehensive search was conducted on the Web of Science Core Collection (WoSCC) database to identify publications related to immunotherapy specifically for the medical imaging of carcinoma. The search spanned the period from the year 2003 to 2023. Several analytical tools were employed. These included CiteSpace (6.2.4), and the Microsoft Office Excel (2016). Results: By searching the database, a total of 704 English articles published between 2003 and 2023 were obtained. We have observed a rapid increase in the number of publications since 2018. The two most active countries are the United States (n=265) and China (n=170). Pittock, Sean J and Abu-sbeih, Hamzah are very concerned about the relationship between cancer immunotherapy and medical images and have published more academic papers (n = 5; n = 4). Among the top 10 co-cited authors, Topalian Sl (n=43) cited ranked first, followed by Graus F (n=40) cited. According to clustering, timeline, and burst word analysis, the results show that the current research focus is on "MRI", "deep learning", "tumor microenvironment" and so on. Conclusion: Medical imaging and cancer immunotherapy are hot topics. The United States is the country with the most publications and the greatest influence in this field, followed by China. "MRI", "PET/PET-CT", "deep learning", "immune-related adverse events" and "tumor microenvironment" are currently hot research topics and potential targets.

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Quantitative MRI cell tracking of immune cell recruitment to tumors and draining lymph nodes in response to anti-PD-1 and a DPX-based immunotherapy

Cited by 7 publications

References 36 publications

Use of Magnetotactic Bacteria as an MRI Contrast Agent for In Vivo Tracking of Adoptively Transferred Immune Cells

Use of Magnetotactic Bacteria as an MRI Contrast Agent for In Vivo Tracking of Adoptively Transferred Immune Cells

HAUS Augmin-Like Complex Subunit 1 Influences Tumour Microenvironment and Prognostic Outcomes in Glioma

Cancer Immunotherapy and Medical Imaging Research Trends from 2003 to 2023: A Bibliometric Analysis

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