Early detection of tumour immune-rejection using magnetic resonance imaging

Hu, De‐En; Da, Beauregard; Mc, Bearchell; Thomsen, Laura H.; Brindle, KM

doi:10.1038/sj.bjc.6600814

Cited by 14 publications

(20 citation statements)

References 45 publications

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“…1 represents a separate, independent experiment. Previous studies have shown that there is a significant increase in immune cell infiltration in those tumors that express ovalbumin and that this increase is even greater in those tumors undergoing immune rejection (32,35,41). This was confirmed in the present study by both flow cytometric (Table 1A) and immunohistochemical analyses (Table 1B) of EL-4 and E.G7-OVA tumors.…”

Section: Resultssupporting

confidence: 77%

“…However, this increased immune cell infiltration was unaffected by host NOS status, being the same in iNOS and eNOS knockout and wild-type mice. We have shown previously (35) that immune rejection in this tumor model is accompanied by vascular proliferation, a feature that has been observed in other tumors undergoing immune rejection. This, too, was unaffected by host NOS status.…”

Section: Resultsmentioning

confidence: 97%

“…We showed previously (35) that the tumorigenicity of this cell line was dependent on its nominal passage number, with early passage cells showing significantly higher levels of spontaneous immune rejection than late passage cells. The incidence of rejection appeared to correlate with the surface expression of ovalbumin determined using flow cytometry, with later passage cells showing lower levels of expression (35). In the later stages of the present study, we recloned some early-passage cells (nominal passage 6) and then selected clones expressing relatively high levels of surface ovalbumin (see "Materials and Methods" section).…”

Section: Resultsmentioning

confidence: 99%

“…In the later stages of the present study, we recloned some early-passage cells (nominal passage 6) and then selected clones expressing relatively high levels of surface ovalbumin (see "Materials and Methods" section). Throughout this study, we have used, in addition to the untransfected EL-4 cell line, this recloned cell line, which expressed relatively high levels of surface ovalbumin and which formed tumors that always underwent spontaneous regression, and the lower expressers used in our previous study (35), which showed variable levels of spontaneous regression. That the regression of tumors expressing high levels of surface ovalbumin was due to immune rejection was confirmed by demonstrating the unrestricted growth of a high-expressing tumor in a severe combined immunodeficient mouse (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…injection of carmine red dye (Sigma; Refs. 34,35). The tumors were then excised postmortem and were fixed in a solution of 10% formalin in saline.…”

Section: Introductionmentioning

confidence: 99%

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Tumor Cell-Derived Nitric Oxide Is Involved in the Immune-Rejection of an Immunogenic Murine Lymphoma

Dyke

Moore

et al. 2004

Cancer Research

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The roles played by host-derived nitric oxide (NO) in the growth and subsequent immune rejection of a immunogenic murine lymphoma were investigated by growing the tumor in mice in which the gene for either inducible NO synthase (iNOS) or endothelial NOS (eNOS) had been ablated. This showed that NO from tumor-infiltrating host cells had no significant effect on either tumor growth or immune rejection, although measurements of tumor nitrite levels and protein nitration showed that there had been significant NO production in the rejected tumors, in both the eNOS and iNOS knockout mice. Inhibition of both tumor and host NOS activities, with an iNOS-selective inhibitor (1400W), a nonselective NOS inhibitor [N-nitro-L-arginine methyl ester (L-NAME)], or scavenging NO with a ruthenium-based scavenger, significantly delayed tumor rejection, while having no appreciable effect on tumor growth. Incubation of tumor cells with medium taken from cultured splenocytes, that had been isolated from immunized animals and activated by incubating them with irradiated tumor cells, resulted in an increase in tumor cell NOS activity and an increase in tumor cell apoptosis, which could be inhibited using L-NAME. We propose that, during the immune rejection of this tumor model, there is induction of tumor NOS activity by cytokines secreted by activated lymphocytes within the tumor and that this results in increased levels of tumor NO that induce tumor cell apoptosis and facilitate immune rejection of the tumor.

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Section: Resultssupporting

confidence: 77%

Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…injection of carmine red dye (Sigma; Refs. 34,35). The tumors were then excised postmortem and were fixed in a solution of 10% formalin in saline.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Tumor Cell-Derived Nitric Oxide Is Involved in the Immune-Rejection of an Immunogenic Murine Lymphoma

Dyke

Moore

et al. 2004

Cancer Research

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Monitoring T‐lymphocyte trafficking in tumors undergoing immune rejection

Kettunen

Brindle

2005

Magnetic Resonance in Med

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Activated T cells, isolated from animals that had rejected a tumor (E.G7-OVA) expressing chicken ovalbumin, were labeled with citrated superparamagnetic iron oxide nanoparticles at an intracellular iron concentration of up to 0.5 pg/cell. Injection of these labeled T cells into animals bearing E.G7-OVA tumors undergoing immune rejection resulted in tumor infiltration of these cells, which was detectable as a heterogeneous decrease in intensity in T 2 -weighted MR images. T-cell infiltration was confirmed by immunohistochemical staining of tumor sections obtained postmortem and was shown to colocalize with iron that had been stained using Prussian blue. Tumor rejection was correlated with the uptake of labeled T cells, since the infiltration of labeled T cells was only observed in those tumors that went on to regress. This technique should assist in the elucidation of those factors that are important in mediating tumor immune rejection.

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Imaging pH with hyperpolarized ¹³C

2011

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pH is a fundamental physiological parameter that is tightly controlled by endogenous buffers. The acid-base balance is altered in many disease states, such as inflammation, ischemia and cancer. Despite the importance of pH, there are currently no routine methods for imaging the spatial distribution of pH in humans. The enormous gain in sensitivity afforded by dynamic nuclear polarization (DNP) has provided a novel way in which to image tissue pH using MR, which has the potential to be translated into the clinic. This review explores the advantages and disadvantages of current pH imaging techniques and how they compare with DNP-based approaches for the measurement and imaging of pH with hyperpolarized (13)C. Intravenous injection of hyperpolarized (13)C-labeled bicarbonate results in the rapid production of hyperpolarized (13)CO(2) in the reaction catalyzed by carbonic anhydrase. As this reaction is close to equilibrium in the body and is pH dependent, the ratio of the (13)C signal intensities from H(13)CO(3)(-) and (13)CO(2), measured using MRS, can be used to calculate pH in vivo. The application of this technique to a murine tumor model demonstrated that it measured predominantly extracellular pH and could be mapped in the animal using spectroscopic imaging techniques. A second approach has been to use the production of hyperpolarized (13)CO(2) from hyperpolarized [1-(13)C]pyruvate to measure predominantly intracellular pH. In tissues with a high aerobic capacity, such as the heart, the hyperpolarized [1-(13)C]pyruvate undergoes rapid oxidative decarboxylation, catalyzed by intramitochondrial pyruvate dehydrogenase. Provided that there is sufficient carbonic anhydrase present to catalyze the rapid equilibration of the hyperpolarized (13)C label between CO(2) and bicarbonate, the ratio of their resonance intensities may again be used to estimate pH, which, in this case, is predominantly intracellular. As both pyruvate and bicarbonate are endogenous molecules they have the potential to image tissue pH in the clinic.

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Early detection of tumour immune-rejection using magnetic resonance imaging

Cited by 14 publications

References 45 publications

Tumor Cell-Derived Nitric Oxide Is Involved in the Immune-Rejection of an Immunogenic Murine Lymphoma

Tumor Cell-Derived Nitric Oxide Is Involved in the Immune-Rejection of an Immunogenic Murine Lymphoma

Monitoring T‐lymphocyte trafficking in tumors undergoing immune rejection

Imaging pH with hyperpolarized ¹³C

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Early detection of tumour immune-rejection using magnetic resonance imaging

Cited by 14 publications

References 45 publications

Tumor Cell-Derived Nitric Oxide Is Involved in the Immune-Rejection of an Immunogenic Murine Lymphoma

Tumor Cell-Derived Nitric Oxide Is Involved in the Immune-Rejection of an Immunogenic Murine Lymphoma

Monitoring T‐lymphocyte trafficking in tumors undergoing immune rejection

Imaging pH with hyperpolarized 13C

Contact Info

Product

Resources

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Imaging pH with hyperpolarized ¹³C